2016 American Neuropsychiatric Association Annual Meeting Abstracts

Background: Aggression following penetrating TBI (pTBI) occurs in up to 1/3 of pTBI patients. The link between frontal lobe lesions and aggression has been demonstrated, however some people with lesions in parts of the brain not generally associated with disinhibition, violence or fear will also show aggressive behavioral changes. It has also been noted that some forms of post-TBI aggression and posttraumatic epilepsy may stem from overlapping network connectivity, leading some to theorize that the brain areas involved in seizures may also play a role in aggression. Objective: Compare patients who developed seizures following pTBI to those who did not develop seizures following pTBI on the Neuropsychiatric Inventory (NPI) aggression subscale to determine if presence of seizures predicts aggressive behavior. Determine if location of lesion has an effect on this correlation. Methods: 159 patients with pTBI were drawn from the Vietnam Head Injury Study registry. Patients with pTBI were divided according to presence (N=69) or absence (N=90) of seizures following injury. Aggression was assessed using the aggression subscale of the NPI. Lesion location was determined using voxel-by-voxel assessment of CTs. Results: A chi-square analysis indicated that patients who developed seizures following TBI were more likely to have elevated NPI aggression scores than patients without seizures (χ² = 9.563, p value=0.003). There was no statistically significant correlation between NPI score and location of lesion in the population with seizures. Conclusion: Patients who developed seizures following pTBI were more likely to engage in aggressive behavior postinjury, regardless of lesion location.

Background: Cognitive difficulties are common in patients with epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no validated treatment exists. We evaluated whether methylphenidate may safely ameliorate cognitive difficulties in epilepsy. We detail here results of the open-label portion of the study. Objective: To evaluate the safety and efficacy of methylphenidate for improving cognition and quality of life in epilepsy. Methods: 30 participants with epilepsy entered a 1-month open-label trial of methylphenidate after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, range 10–20mg BID. Measures included: Beck Depression (BDI) and Anxiety Inventories (BAI), Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist (SSC), Adverse Events Profile (AEP), Quality of Life in Epilepsy-89 (QOLIE-89), Conners Continuous Performance Task (CPT), Symbol-Digit Modalities Test (SDMT), and the Medical College of Georgia Memory Test (MCG). 14 healthy, nonmedicated controls were tested concurrently. Results: 28 participants (13 men/15 women) finished. Withdrawals occurred due to anxiety (N=1) and fatigue (N=1). Mean age=36.4 (range=20–60). Epilepsy types were: focal (N=21), generalized (N=6), or unclassified (N=1). Mean epilepsy duration=12.3 years, and mean baseline seizure frequency=2.8/month. There were significant improvements (paired 2-tailed t tests) on methylphenidate for SDMT, MCG, CPT (d', hits, HRTSD, omissions, commissions, and variability), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language) (all p≤0.003). BDI and additional subscales also improved (all p≤0.026). Statistical improvements were greater than controls. Seizure frequency was not altered by methylphenidate. Conclusions: Methylphenidate may be an effective and safe option for improving cognitive deficits and quality of life in epilepsy.

Background: The amyloid cascade theory which purports overproduction and/or reduced clearance of Amyloid-Beta (Aβ) as etiologic in late-onset Alzheimer’s Disease (LOAD). However, these processes may reflect downstream biologic events in LOAD genesis. Recent research has suggested that aging, vascular burden and inflammatory processes play important roles well in advance of amyloid and tau deposition and far in advance of clinical symptoms. Objective: Review of risk factors for LOAD which converge to dysregulate mitochondrial energy transduction. Methods: PubMed, EMBASE, and Medline were searched using (Alzheimer’s -risk factors –inflammation- mitochondria- vascular). Relevant manuscripts were reviewed to generate a coherent hypothesis of converging risk factors leading to disruption of mitochondrial function. Results: Age is the primary risk factor. Vascular risk factors include hypertension, hyperlipidemia, diabetes and ApoE4. Recurrent depressive episodes and their association with cortisol dysregulation confer increased risk. Vascular burden is associated with subcortical CNS ischemic changes. Recurrent depressive episodes are associated with microvascular changes and with cortisol dysregulation which is neurotoxic. These events promote increases in inflammatory mediators. Reduction in proton-motive force and inability of mitochondria to buffer against reactive oxygen species (ROS) result. Mitochondrial DNA (mtDNA) is damaged by close proximity to ROS at the site of electron transport. There is insufficient energy for clearance of soluble Aβ into the CSF, which activate microglia- mediated inflammation. Tau hyperphosphoryllation and deposition of amyloid result, perhaps through up-regulated GSK-3β. Activation of caspases leads to neuronal apoptysis. Conclusion: Deposition of amyloid and tau are likely down-stream events resulting from energy depletion.

Background: Post-TBI bipolar mania can present with subthreshold manic symptoms. Post-TBI neuropsychiatric disturbances of impulsivity, distractibility, and aggression occur more commonly and can distract from making a bipolar diagnosis. First-line treatment for these neuropsychiatric disturbances are with SSRIs, which may worsen manic symptomatology. This case underscores the importance of including post-TBI bipolar disorder on the differential diagnosis in patients with post-TBI neuropsychiatric disturbances, even when threshold manic symptoms are not present. Case History: A 31 year old man with preinjury history of major depression, ADHD, and alcohol use disorder sustained mild TBIs in 2008, 2012, and 2013. He came to our neuropsychiatry clinic due to worsening depressive symptoms and aggression his last TBI. Prior to his injury, he had remission of major depression with an SSRI. He had no history of mania and was prescribed several antidepressants, each requiring discontinuation due to adverse reactions of increased irritability. Bipolar disorder was suspected after three antidepressant trials having similar effect. He was then started on valproic acid which resulted in resolution of his aggression. Depressive symptoms persisted and a cross-titration of valproic acid to lamotrigine successfully treated his depression without reemergence of aggression. Conclusions: Several complications made his diagnosis unclear, including his alcohol use disorder and ADHD, although the most important was the lack of clear manic symptoms with history of successful treatment of depressive episodes with an SSRI prior to his last mild TBI. A lower threshold may be required for treating subthreshold manic symptoms in patients with mild TBI.

Background: Patients with intellectual disabilities commonly present to neuropsychiatry clinics due to behavioral disturbances secondary to psychiatric disorders. Genetic testing using Single Nucleotide Polymorphism (SNP) array can detect underlying etiologies and change clinic practice. This case highlights the importance of the SNP array in the routine clinical care of patients with intellectual disabilities and behavioral disturbances. Case History: A 21 year old woman with autism and mild intellectual disability was brought to our neuropsychiatry clinic by her residential home staff for management of impulsive physical aggression. Her history was also consistent with bipolar disorder although her aggression seemed to occur during periods of euthymia. She had previously been prescribed quetiapine and lorazepam which we ineffective in reducing her symptoms. SNP array analysis revealed a deletion in chromosome band 5q34 in the region coding the GABRG2 gene. This gene encodes the GABA-A β2 subunit and is associated with epilepsy and febrile seizures. Other GABA-A subunits mutations have been associated with intellectual disability, autism-spectrum disorder, and also bipolar disorder. Our initial treatment plan involved tapering lorezapam which was suspected to be contributing to her aggression through disinhibition. After the genetic testing we decided against this taper and are considering the possibility of using GABA reuptake inhibitor, tiagabine. Discontinuation of the lorezapam could have resulted in worsening of her epilepsy and possibly worsening of her neuropsychiatric disturbances. Conclusions: Although not commonly used in psychiatric clinical practice, SNP array can provide useful clinical data when used in patients with intellectual disabilities with neuropsychiatric disturbances.

Background: Age’s effect on cognition is largely mediated by the latent variable “δ” (for “dementia”).¹ Age’s effects on cognition are potentially “dementing”^2,3. Serum Insulin Like Growth Factor Binding Protein 2 (IGF-BP2) is strongly associated with age-specific cognitive change.⁴ Objective: IGF-BP2 binds Serum Insulin Like Growth Factor -1 (IGF-I). IGF-1 declines with age, and is associated with cognitive performance.^5,6 Here we test IGF-1 as a potential mediator of age’s specific effects on δ. Methods: Structural equation models (SEM) was used in the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort (n=3072) and conducted in Analysis of Moment Structures (AMOS). IGF-1 levels were determined at baseline. We used an ethnicity equivalent δ homolog wave 2 [dEQ(w2)]. Thus, the model is longitudinal and arguable causal. Results: Model fit was excellent [χ²= 20.661(19), p=0.356; CFI=1.0; RMSEA=0.005]. Serum IGF-1 was found to mediate 21.5% of age’s association with dEQ(w2) scores (p<0.001) [Table 1]. Conclusion: IGF-1 is found to be a significant partial mediator of age’s effect on δ. Serum IGF-1 levels protect against dementia but decline with age.

1. Royall DR, Palmer RF, O’Bryant SE; Texas Alzheimer’s Research and Care Consortium: Validation of a latent variable representing the dementing process. J Alzheimers Dis 2012; 30:639–649

2. Gavett BE, Vudy V, Jeffrey M, et al: The δ latent dementia phenotype in the uniform data set: Cross-validation and extension. Neuropsychology 2015; 29:344–352

3. Palmer RF, Royall DR: Future Dementia Status is Almost Entirely Explained by the Latent Variable δ’s Intercept and Slope. J Alzheimers Dis (in press)

4. Royall DR, Bishnoi RJ, Palmer RF: Serum IGF-BP2 strongly moderates age’s effect on cognition: a MIMIC analysis. Neurobiol Aging 2015; 36:2232–2240

5. Aleman A, Verhaar HJJ, De Haan EHF, et al: Insulin-like growth factor-I and cognitive function in healthy older men. J Clin Endocrinol Metab 1999; 84:471–475

6. Aleman A, Torres-Alemán I: Circulating insulin-like growth factor I and cognitive function: neuromodulation throughout the lifespan. Prog Neurobiol 2009; 89:256–265

Background: The neuropsychiatric manifestations secondary to cerebrovascular accidents – e.g. frontal lobe syndrome (FLS) - are clinically relevant. Interestingly, damage to the frontal lobe can be extremely detrimental and may complicate the clinical management. Impaired executive functions, apathy, impulsivity are hallmarks of frontal circuit dysfunction secondary to vascular event. Accordingly, this case illustrates the usefulness of Lurasidone for the management of refractory depression with associated apathy and lability in FLS. Case History: In this case, a 65 y/o Hispanic-male who was complaining of depressive and liable mood, impulsivity, poor-sleep and judgment, irritability with frequent anger outbursts, crying spells without apparent reason, cantankerous and risk taking behavior, as well, as paranoid ideations status post frontal lobe aneurysm two years prior. Patient was also evaluated by neurosurgery team and brain MRI which showed previous vascular accident. Symptoms of unpredictability and poor-judgment with FLS, along with his previous psychiatric history, made it difficult to treat as the patient had been unsuccessfully treated with conventional treatments including mood stabilizers, SSRI’s, and Benzodiazepines. Patient was started on Lurasidone 40 mg, which is currently approved for Depression related to Bipolar Disorder, with eventual improvement of FLS induced neuropsychiatric manifestations with Depression as the most prominent symptom. Conclusions: FLS is a difficult condition to treat, especially in patients with previous psychiatric history. This case highlights potential effective pharmacotherapy for managing the depressive and labile mood when conventional treatments fail. Prospective-randomized clinical trials are recommended to evaluate the efficacy of Lurasidone in FLS.

Background: Differentiating bipolar disorder (BD) from major depressive disorder (MDD) solely on clinical grounds is challenging; the consequences of misdiagnosis on treatment and prognosis are substantial. Neuroimaging, particularly resting state functional connectivity (rsFC), may facilitate appropriate diagnosis, especially if focused on connectivity within networks subserving emotional regulation that are likely differentially affected across mood disorders. Objective: This study sought to compare rsFC in specific regions of interest (ROIs) involved in emotional regulation between BD and MDD. Methods: We examined patterns of rsFC among inpatients with SCID-I confirmed diagnoses of BD (N=36) or MDD (N=135). A priori emotion-regulation related ROIs included superior, medial and inferior frontal gyri, anterior cingulate cortex (ACC), amygdala, insula, and striatum. Statistical significance was Bonferroni-corrected and set at p=0.0014. Results: Analysis of covariance, controlling for gender and age, demonstrated lower connectivity between the ipsilateral inferior frontal gyrus and insula in BD (M = 0.159, SD=0.230) than MDD (M = 0.280, SD=0.191), F[3, 171] = 10.72, p=0.0010. These findings were lateralized to the left hemisphere. Differences between patients diagnosed with BP and MDD also were found between the medial frontal gyrus and insula, both ipsilaterally (p=0.011) and contralaterally (p=0.012); these differences did not reach statistical significance after Bonferroni correction. Conclusion: BD and MDD differed in rsFC within a left-hemisphere inferior fronto-insular network involved in emotional regulation. Further studies of this and related rsFC emotional regulation network differences between these conditions are needed.

Objective: To refine understanding of the neuroanatomical basis of asomatognosia. Background: The era of hyper-acute stroke treatment affords a fresh perspective on the classically described neurobehavioral disorders: early assessment hours after stroke can help clarify the natural history, and neuroanatomical basis of syndromes originally described in the subacute phase. Here, we applied this to asomatognosia, a disorder of bodily awareness that results in the misidentification of one’s limb (LM). Design/Methods: We assessed 27 patients within 24 hours of acute right MCA stroke and then with daily exams for seven days. LM was determined by asking the patient “whose hand is this?” while holding the patient’s hand in the ipsilesional hemispace; patients either correctly identified the limb (CL), or misattributed ownership of it (LM). Voxel-based lesion analysis was performed to investigate which brain regions are associated with LM. Results: Limb misidentification is common in the hyperacute phase (52%), but is a rapidly improving phenomenon with 22% exhibiting LM on day 3; 11% on day 7. Lesion analysis showed the inferior parietal lobe as the region damaged significantly more often in patients with LM (FDR corrected level of p=0.05, z value greater than 3.26). Conclusion: Limb misidentification is a transient phenomenon associated with injury to the inferior parietal lobe. Because prior anatomical studies examined patients many days after stroke, they likely misclassified many patients with asomatognosia who had simply improved by the time of examination. Thus, hyper-acute assessment is an important way of improving sensitivity in lesion symptom analysis.

Introduction: We present a case report of a patient with no significant psychiatric history other than two manic episodes related to fentanyl use. Case Presentation: Patient is a 26 year old Caucasian female with history of chondro-calcinosis presenting with manic symptoms. She has congenital chondro-calcinosis, requiring hip surgery four times. Two of these surgeries were pretreated with fentanyl patch for presurgical pain management, which was removed prior to surgery. Symptoms of mania developed after starting on fentanyl both times. Patient was treated with mood stabilizers following first manic episode which were then tapered off. Patient did well until the second time she used a fentanyl patch for her 4th surgery. Patient was admitted to psychiatric unit following surgery for aggression, agitation toward family members and hypomanic symptoms that included hyper-talkativeness, grandiosity, and a flight of ideas. She was difficult to redirect and was sleeping approximately only two hours per night. Patient was initially treated with quetiapine with not much improvement. Later we added mood stabilizer, valproic acid. Patient then showed significant improvement and was discharged home. Conclusion: Fentanyl is one of the most common drugs used for pain control. Its use is associated with common adverse effects such as respiratory depression, confusion, sedation, fatigue, bradycardia, constipation. Mood symptoms can also be associated with fentanyl use. However there are few reported cases of manic episodes secondary to fentanyl use. Our patient’s manic episodes had a clear temporal association with fentanyl use.

Background: Intracerebral Hemorrhage (ICH) survivors are at high risk for depression, presumed to represent Vascular Depressive Disorder (VDD) due to the role played by Cerebral Small Vessel Disease (CSVD) in ICH etiology. However, risk factors and prognostic relevance of post-ICH depression have not been systematically investigated. Objective: We sought to identify predictors of post-ICH depression and clarify its prognostic relevance for long-term cognitive decline. Methods: We enrolled and longitudinally followed 252 ICH survivors with no prior history of mood disorder. Exposure variables of interest included baseline clinical information, as well as CSVD genetic risk factors (APOE variants ε2 and ε4), and CSVD imaging manifestations (white matter disease [WMD], silent lacunar infarcts [SLI], cerebral microbleeds [CMB]). We captured outcomes (incident depression and cognitive function) during follow-up using validated scales administered via telephone every 6 months. Results: A total of 100 / 252 ICH survivors (39.6%) developed new-onset mood disorder during an average follow-up time of 49.6 months (Inter-Quartile Range [IQR]: 29.3–59.7). Risk factors for post-ICH depression in multivariable Cox analysis included lower educational achievements, APOE ε4, and moderate/severe WMD (all p<0.05). Depression preceded post-ICH cognitive impairment in 53 / 110 individuals with new-onset dementia (48%, 95% CI 38%−56%, p=0.006), with median anticipation of 17.6 months (IQR=12.6–23.2). Conclusion: Post-ICH depression affects a large proportion of ICH survivors, and its association with CSVD suggests that VDD represents the underlying etiology for new-onset mood symptoms. VDD often heralds impeding cognitive impairment after ICH.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for medication-refractory major depressive disorder, yet the mechanisms of action for this intervention are poorly understood. Objective: Here we evaluated cerebral cortex morphology in response to rTMS treatment, and specifically whether morphological changes could be used as a biomarker of treatment response to distinguish responders from nonresponders. Methods: 38 patients with medication-resistant major depression, 30 female, age 46 +/− 14, received a 4–6 week course of left dorsolateral prefrontal cortex (L DLPFC) 10 Hz rTMS. MRI and Hamilton Depression Rating Scale (HamD) were acquired before and after treatment. The longitudinal processing stream of FreeSurfer was used to optimize detection of changes in cerebral cortex thickness in the same individual across two time points, before and after rTMS. Results: Depression symptoms improved from pre- to postrTMS across the 38 patients (24 +/− 7 to 15 +/− 8; p<0.001). There were no global changes in overall cortical volume or average cortical thickness. A comparison of cortical thickness difference from pre- to postrTMS between responders (N=14) and nonresponders showed a significant increase in thickness of the left dorsomedial prefrontal cortex in responders relative to nonresponders, p<0.001, uncorrected for multiple comparisons. Conclusions: Increased left DLPFC thickness is associated with effective rTMS treatment for major depression and may serve as a biomarker of treatment, distinguishing responders from nonresponders. Future work aims to increase the sample size as well as explore whether structural measures in the baseline MRI can predict response to rTMS treatment.

Background: Neurodevelopmental disorders (NDDs) are among the greatest threats to childhood health globally. Epilepsy and autism are two of the most prevalent and debilitating NDDs. Importantly, these co-occur in approximately 30% of children with a primary diagnosis of either disorder, suggesting a common brain pathology. Studies of NDDs have consistently shown that early intervention leads to better long-term outcomes. Yet, early intervention is predicated on early detection. Objective: We test the hypothesis that methods from complex dynamical systems theory based on multiscale recurrence plot analysis (mRPA) may be used to analyze short EEG measurements as reliable biomarkers for autism or absence epilepsy. Methods: Data from 92 children collected from a research lab and the Epilepsy Clinic at Boston Children’s Hospital were analyzed retrospectively. Nonlinear complexity measures were computed and machine learning algorithms were used in a cross-validation study to determine classification accuracy. Similarities and differences between autism and absence epilepsy were also found. Results: Classification algorithms were able to distinguish 3 groups (absence, ASD, control) with nearly 100% accuracy. Important differences between absence epilepsy and autism groups may give insight into functional brain pathologies in these disorders, including possibly common neuropathologies and differences. Conclusion: Analysis of EEG signals with mRPA may provide a useful and urgently needed biomarker for early detection, monitoring developmental trajectories, predicting severity and potentially guiding early treatment of emerging epilepsy or autism in children. The finding that autism values were intermediate between epilepsy cases and controls suggests a common pathological continuum that is measureable.

Background: MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) is a progressive neurodegenerative disorder. The most common psychiatric presentations are depression and anxiety. Psychosis is seldom found initially and no published case reports describes late onset psychosis in a patient with rapid cognitive decline. Psychiatric symptoms, usually in the third decade of life, prompt investigation of mitochondrial cytopathies. Later, patients may develop cognitive impairment, strokes, seizures, and diabetes. MRI classically demonstrates basal ganglia calcifications and/or strokes that do not obey vascular territories. Case History: 46 year old male with history of diabetes from MELAS, anxiety, and recent cognitive decline. He was admitted after being found in traffic with scars suggestive of self-mutilation. On admission, he was manic, delusional about his cat causing his MELAS, and demonstrating auditory hallucinations. MRI demonstrated iron deposition in the basal ganglia. Psychosis was refractory to antipsychotic medications, but his behavior improved with administration of levocarnitine and arginine. He remained paranoid on discharge. Conclusion: Literature has linked brain iron deposition with neurodegenerative disease and aging. Mitochondrial diseases are frequently associated with cognitive decline but have yet to be investigated in this regard. With the oxidative stress endured by the brain in patients with mitochondrial cytopathies, and the role of this stress on iron uptake, one would expect concomitant MRI findings. There may be an underestimation of iron deposition which could serve as a marker for cognitive decline in MELAS. Atypical presentation of psychosis in patients with MELAS may be refractory to antipsychotics. Therapy should be considered with levocarnitine and arginine.

Background: Profound and sustained hypoglycemia shifts brain metabolism from aerobic to anaerobic, producing functional hypoxic injury and encephalopathy. Few reports describe the clinic-radiologic correlations of such injuries using serial magnetic resonance imaging (MRI) findings. We present such a case. Case History: A 58-year-old woman with type II diabetes mellitus and no prior neurological problems was found unresponsive with a blood glucose of 20. Her level of arousal improved after correction of blood glucose, but she remained severely encephalopathic throughout her acute and inpatient rehabilitation hospitalizations. Arousal and selective attention were reasonably normal, but sustained attention, communication, and higher cognition were profoundly impaired. She also exhibited diffuse hyperkinetic movements, best characterized as combined choreoathetosis and motor restlessness, during most waking hours throughout her hospital stays. Extensive workup revealed no other contributing etiologies, such as seizures or autoimmune encephalitis. Early DWI and T2/FLAIR MRI demonstrated bilateral diffuse cortical ribboning (lateral greater than medial) and symmetric striatal hyperintensities (caudate more than putamen); these findings remained on MRI performed 9 and 76 days postinjury. Conclusions: This patient’s profound and sustained hypoglycemia produced a pattern of cortical and subcortical similar to that produced by hypoxia-ischemia (especially histotoxic hypoxia), and her cognitive and motor abnormalities corresponded to MRI-demonstrated areas of injury. Cortical ribboning and striatal hyperintensities on MRI appeared immediately after the hypoglycemic injury and persisted for at least the next two months. Previous reports describe an association between persistent gray matter changes and poor prognosis after hypoglycemic brain injury, consistent with this patient’s course.

Background: Major Depressive disorder (MDD) is frequently resistant to multiple modes of treatment including several medication classes and therapy modalities. For patients with treatment resistant depression (TRD), electroconvulsive therapy (ECT) is considered the most effective next step in management. However, when patients fail ECT treatment due to either nonresponse or adverse side effects, there is no definitive alternative. Repetitive Transcranial Magnetic Stimulation (rTMS) is an alternative intervention for TRD, but generally has a lower response rate compared with ECT. However, it is noninvasive and has very few adverse effects. Therefore, it has filled a niche for the ECT-averse but its use for ECT-resistant depression has not been thoroughly studied. Case History: Three patients diagnosed with MDD who all failed multiple medication trials, right unilateral (RUL) and bilateral (BL) ECT but responded to treatment with rTMS with a 50% or greater reduction in symptoms as rated by their MADRS scores. Conclusion: All three patients showed minimal response to standard treatment with both RUL and BL ECT and had to discontinue ECT due to cognitive side effects. For these patients, rTMS was better tolerated and more effective than ECT in treating their depressive symptoms. One common thread between the patients was the presence of multiple psychiatric diagnoses with double depression: MDD and Dysthymia, and combat related PTSD. This case series hopefully adds to the preliminary literature that is demonstrating the effectiveness of rTMS in ECT-resistant MDD. At this time, more rigorous research is needed to determine where rTMS therapy should fall in the treatment algorithm for treatment-resistant depression.

Background: Associations among subjective cognitive concerns, mood, objective memory, and personality have been explored in the literature, though results have been mixed. Boyle et al. (2010) found depression did not moderate the association between personality and cognition. Pearman and Storandt (2004) found associations among these factors but only used one memory task for objective cognition. Objective: Combining aspects of multiple studies in a large sample, the current study sought to explore the impact of memory, executive functioning, mood, and neuroticism on subjective memory concerns. Methods: Data were obtained from participants who completed the Midlife in US Study (MIDUS) surveys, a nationally representative sample of English-speaking adults within the United States. Data were collected via telephone interviews and self-administered questionnaires returned by mail. The current study used data from the study’s Wave II (M=3272). Neuroticism was measured by the NEO Five-Factor Inventory. Depression and anxiety were measured by patient self-report. Subjective memory complaint was measured by asking, “Compared to other people your age, how would you rate your memory?” Results: Multiple regression analyses revealed that depression, anxiety, objective cognition (composites of episodic memory and executive functioning), and neuroticism all significantly predicted the presence of subjective memory concerns (R²=0.109; ps<0.001). Conclusion: Factors predicting patient concerns about memory were explored. While objective memory performance as well as depression and anxiety significantly predicted subjective complaints, executive functioning and neuroticism emerged as the strongest predictors. Thus, clinicians whose patients express concerns about memory performance should also consider mood and personality beyond cognitive screening alone.

Background: Telemission and telepathy as an isolated delusional disorder in the absence of schizophrenic symptoms has not heretofore been reported. Case History: A 28 year old, single male presented with the belief that he could read other peoples minds and they could read his. During college, while using marijuana he began experiencing these delusions, which continued despite cessation of marijuana. After admitting to delusions as part of a routine pre-employment screening, he was referred for evaluation. The delusions were initially constant but have waned to twice a day lasting seconds and are sequentially linked—first the telemission followed by the telepathy. The symptoms are present when the patient is in proximity of at least two people. Telepathy occurs while using the telephone but not with written communication. The fear of thought-broadcasting socially unacceptable thoughts makes him avoid social encounters. He reassures himself that this has not occurred based on lack of reaction from others. He admits to déjà vu and clairvoyance but denies Schneiderian symptomatology. Examination: Well groomed, cooperative, engaged, displaying appropriate humor, normal mood, congruent affect and goal directed thought processes with insight regarding his delusions. While atypical antipsychotics were successful in the past, the patient declined these because the symptoms are now mild. Conclusion: This patient does not meet the DSM-5 criteria of schizophrenia. Google scholar and PubMed search yielded no publications describing concurrent isolated delusions of telepathy and telemission. This highlights the importance of screening highly functional individuals for underlying delusional disorders.

Background: There are multiple case reports of cabergoline, a dopamine receptor agonist on D₂ receptors used in treating prolactinomas, causing decompensations in previously stable patients with known psychotic disorders. This case demonstrates a unique presentation of new onset cabergoline-induced psychosis in a patient with intellectual disability. Case History: Patient CT is a 29 year old female with a history of cerebral palsy, seizures, and severe IDD. She had a history of treatment for “anxiety” with low-dose fluvoxamine. Epilepsy was present and was controlled with lamotrigine. Further mental status changes resulted in MRI, which demonstrated pituitary adenoma. One month after initiation of treatment with cabergoline, patient developed disrupted sleep and night-time behavioral changes. Family reported concern for responding to internal stimuli. Patient was admitted to endocrinology service, cabergoline was discontinued and she was seen by neuropsychiatry consult. Risperidone at bedtime was started with some benefit. Once home, sleep disturbance continued, and spells were demonstrated as stereotyped, suggesting epileptiform activity. Admission to the epilepsy monitoring unit resulted in a few small spells being captured on EEG with no epileptiform discharges but a background of excessive beta activity. Conclusion: This case demonstrates a decompensation in a nonverbal patient when being treated with a dopamine receptor agonist. Symptoms demonstrated have been suggestive of psychosis or nighttime frontal epileptiform activity. These symptoms have been resistant to treatment with multiple psychotropics as well as behavioral interventions. This case demonstrates the multiple, unintentional neuropsychiatric impacts of modulation of the dopamine system with nonpsychiatric medications. (Video of nighttime spells is available.)

Background: Similar to persons with other neuropsychiatric illnesses, persons with catatonia may have normal electroencephalogram (EEG) patterns, abnormal EEG patterns associated with a general medical or neurologic condition, or abnormal EEG patterns of unclear significance. Formal studies of EEG findings in catatonia are very limited, exclude persons with neurologic or general medical conditions, and do not account for electrographic effects of medications. Objective: To examine EEG findings in adults with catatonia. Methods: We performed a retrospective chart review of all patients admitted over a four-year period to an adult acute inpatient psychiatry service of a university hospital. We reviewed all EEG studies obtained as part of the routine clinical care of all patients identified as catatonic by the treating physician. We assessed the association among clinical features and EEG patterns using Chi-square and linear regression analyses and accounted for exposure to medications that have potential electrographic effects. Results: Thirty-eight (31%) of 121 persons with catatonia underwent EEG, thirty of which were obtained while the person was catatonic. Ten of these studies (33%) were normal. Of the 20 abnormal studies, EEG patterns included focal slowing, diffuse slowing, focal and diffuse slowing, sharp waves, and spikes. Twenty persons (66%) had been exposed to antipsychotic medication. Specific EEG patterns were not statistically associated with clinical diagnosis or the observed short-term outcome of catatonia. Conclusions: A majority of adults with catatonia may have abnormal patterns on EEG, but these abnormalities may not be specific to catatonia, its underlying causes, or its outcome.

Background: Case reports, an important resource in medical education for centuries, are currently frowned upon in psychiatric publishing in favor of evidence-based population studies, metaanalyses, and controlled trials. While the latter remain the gold standard for learning about the natural history, neuroanatomic localization, pathophysiology and treatment of disease, the well-described single case study remains a useful tool in neuropsychiatric education. Case reports illustrating unusual presentations of common disorders or describing uncommon disorders are a critical component of neuropsychiatry education. Objective: Describe several cases in neuropsychiatric history that are of particular importance because they both carefully describe a syndrome and teach modern neuropsychiatrists valuable lessons that continue to be relevant. Methods: Review of the literature revealed no concise listing of these seminal cases. We reviewed numerous case reports and asked a number of leading figures in neuropsychiatry and behavioral neurology for their opinions as to the most important cases in the history of neuropsychiatry. We then selected a small number of cases to describe as a core body of case literature for use by neuropsychiatry trainees seeking to understand the history of brain-behavior correlations. Results: Cases selected for review include: Phineas Gage, HM (anterograde amnesia following bilateral anteromedial temporal lobectomy), Tan Tan (Broca's index case), GK (Price and Mesulam’s early-life frontal trauma case), JP (Ackerly and Benton’s developmental frontal case), Auguste Deter (Alzheimer's case), Solomon Shereshevsky (Luria's mnemonist), and AJ (Parker et al's case of superlative autobiographical memory). Conclusion: These cases and others like them remain important as one component of the education of modern neuropsychiatrists.

Background: The most common neuropsychiatric symptoms of Huntington Disease (HD) include mood symptoms, personality change, psychosis, and dementia. Mood and personality changes are the initial manifestation in about one third of affected people. Three-11% develop psychosis, usually associated with cognitive impairment and well after the development of motor symptoms. There are few case reports of patients with psychotic symptoms that predate motor symptoms in HD. Case History: A 29-year-old right-handed male with genetically confirmed Huntington Disease was admitted to a public sector inpatient facility with recurrent psychosis since age 27 and suicidal ideation. Evaluation was notable for latency of response, response to internal stimuli, thought blocking, paranoia, and suicidal ideation with plan. He was stabilized on olanzapine and referred for a neuropsychiatric evaluation due to diagnosis of HD. He had no subjective reports of abnormal movements. Family history was significant for mother diagnosed with HD at age 35, and deceased at age 52. Exam was significant for concrete thought process, poor effort on bedside cognitive testing, decreased verbal fluency, and poor attention to detail on 5-minute recall of an asymmetric complex figure. Neurologic examination was otherwise completely normal, with a score of zero on the motor portion of the Unified Huntington’s Disease Rating Scale. Conclusions: This case may represent an unusual clinical presentation of psychosis as an early symptom of HD versus coincident schizophrenia. HD should be included in the differential diagnosis of patients presenting with psychosis even without any apparent motor symptoms.

Background: Kahlbaum originally described catatonia as its own entity with associations to other illnesses in 1874. Later, Kraepelin described it as a type of schizophrenia which has persisted to date. Not until the DSM-5 was catatonia no longer a subset of schizophrenia. Catatonia is generally considered secondary to either a psychiatric or medical illness, despite case reports of primary catatonia without other illness. Gjessing described periodic catatonia which involves rapid-onset, brief, recurrent episodes of hypokinetic or hyperkinetic catatonia and is generally asymptomatic between episodes. Case History: We present two cases of patients with recurrent, severe catatonia, without known cause. Patient one is a 24 year-old African American woman with no past psychiatric/medical history with repeated episodes of catatonia responsive to lorazepam and electroconvulsive therapy (ECT). Patient two is a 24 year old African American man with no past psychiatric/medical history who also experienced multiple episodes of catatonia unresponsive to and worsened with neuroleptics but, as in the first case, responsive to lorazepam and ECT. Extensive laboratory testing, including genetic microarrays and imaging revealed no underlying cause of catatonia in both patients. Although there is evidence of genetic transmission of periodic catatonia, no genetic etiology was found in our cases. Conclusion: Our patients, as well as reports in the literature, support the existence of a diagnosis of idiopathic periodic catatonia. This has not yet been reflected in diagnostic systems and can result in misdiagnosis, inadequate or inappropriate treatment, and poor patient outcomes.

Background: Autism spectrum disorders are neurodevelopmental disorders in which social communication and interactions are impaired in multiple contexts. This can also include repetitive behaviors or motor movements and hyper- or hypo-reactivity to sensory input. Catatonia is a syndrome with well described motor phenomena that can overlap with motor behaviors noted in autism. Both of these conditions have been putatively linked to genetic mutations on chromosome 15. Case History: Patient is a 19 year-old African American man with a past psychiatric diagnosis of bipolar I disorder and autism and a history of childhood seizures was admitted to psychiatry for abnormal hypersexuality, severe hyperactivity and impulsivity. On presentation, he exhibited features of autism including poor eye contact, limited social interactions, and repetitive hand-flapping movements as well as signs of catatonia including mutism, impulsivity, utilization behaviors, negativism, grimacing, mitgehen, and gegenhalten. Patient’s symptoms of catatonia partially improved with benzodiazepine treatment. However, after receiving a course of ECT to fully treat his catatonic symptoms, his apparent symptoms of autism resolved. He is now maintained as an outpatient on lithium and has no social impairment. Conclusions: To our knowledge, this is the first case reported in which a patient had chronic catatonia which presented as an autism spectrum disorder and with treatment of catatonia, the autistic symptoms fully resolved. Although both of these syndromes could be explained by a genetic mutation on chromosome 15, our patient showed no known mutations.

Background: Cognitive impairment occurs in 30%−50% of HIV-infected patients well maintained on cART. Objective: Determine the association between performance in specific cognitive domains and brain structure in women with HIV. Methods: Women were recruited from the Brooklyn site of the Women’s Interagency HIV study. Participants received a battery of cognitive tests every 2 years including the Hopkins Verbal Learning (HVLT), Stroop, experimental span, pegboard, symbol-digit, fluency, and trails A and B tests. 3T MRIs were obtained within 6 months of cognitive testing. We used factor analyses to reduce the number of cognitive measures from 11 to 4, and measured the correlation between these factors and brain structure. Results: Forty-four women (30 HIV-infected and 14 uninfected) were included. HIV-infected women did not differ from uninfected in age, reading score, or on any of the cognitive measure or MRI measures. ‘Episodic memory’ (HVLT scores) loaded on factor 1, ‘concentration’ (experimental span) on factor 2, ‘speed’ (pegboard as well as Stroop interference) on factor 3, and ‘education’ (WRAT & fluency) on factor 4. The 4 factors explained 73% of the variance. The ‘concentration’ factor was associated with mean diffusivity (−0.32, 0.04). The ‘speed’ factor was associated with cortical volume (R=−0.49, 0.002). The ‘episodic memory’ factor and the ‘education’ factors were not associated with any of the MRI measures. Conclusion: A factor that may represent speed was associated with cortical and subcortical volumes. A factor that may represent concentration was associated with mean diffusivity.

Background: Even among patients well treated with cART, cognitive impairment is found in 30%−50% of patients with HIV. Altered white matter integrity may be one substrate accounting for cognitive impairment. Vascular disease and inflammation have been proposed as possible contributors to white matter changes. Objective: To determine whether C-reactive protein (CRP) is predictive of white matter changes in women with HIV. Methods: Women were recruited from the Brooklyn site of the Women’s Interagency HIV study. 3 T MRIs, middle cerebral artery velocity as determined by transcranial Doppler, and retinal fractal dimension were obtained on 88 women, 2/3 were HIV-infected. A subset of 38 of these women also had had CRP measurement 10 years before the MRI and vascular evaluations. We tested whether the vascular predictors and CRP were associated with white matter outcomes using general linear models. Results: Women were 45.8 (SD=7.1) years old. In general linear models that included age, top quartile of CRP, hypertension, middle cerebral artery velocity, intracranial volume, and arterial and venous fractal dimension, the top quartile of CRP was weakly associated with mean diffusivity (F=3.5, p=0.07), but not with fractional anisotropy or abnormal white matter volume. Both middle cerebral artery velocity (F=6.1, p=0.02), and arterial fractal dimension (F=4.8, p=0.04) were also associated with mean diffusivity. Conclusions: Chronic inflammation and vascular disease may both contribute to white matter changes in women with HIV.

Background: The cerebellar cognitive affective syndrome (CCAS) is characterized by deficits in executive function, visual spatial processing, linguistic communication and affect regulation. The neuropsychiatric features of the CCAS have been conceptually grouped into five domains: attentional control, emotional control, autism spectrum, psychosis spectrum, and social skills, with symptoms reflecting positive (exaggerated) or negative (diminished) responses (Schmahmann, Weilburg, & Sherman, 2007). Objectives: 1) Develop an informant-based scale to assess the neuropsychiatric symptoms of CCAS. 2) Explore construct validity based on a priori hypotheses of symptom domains. 3) Examine the psychometric properties of the CNRS and refine for future clinical use. Methods: 21 adults with cerebellar disease identified an informant to complete the CNRS, the Neuropsychiatric Inventory Questionnaire (NPI-Q), the Behavior Rating Inventory of Executive Function (BRIEF), and the Adult Behavior Checklist (ABCL; ages 18–59) or the Older Adult Behavior Checklist (OABCL; ages 60–90+). Hypothesized scale structure, internal consistency (Cronbach’s α), and associations with validity measures were evaluated. Results: The CNRS subscale structure was generally confirmed. Cronbach’s α was>0.70 for all but one domain (Autism Spectrum). Of the Spearman’s correlations between CNRS and validity subscales, 17 out of 22 reached statistical significance (p<0.05) and 18 exceeded the 0.50 threshold indicating moderate associations. Conclusions: These results indicate that the CNRS is a reliable and valid rating scale for assessing the neuropsychiatric symptoms that comprise the affective component of the CCAS (Schmahmann syndrome). Future studies are planned in larger cohorts of cerebellar patients including clinical and healthy comparison groups.

Objective: To determine whether the abnormal belief content in Capgras delusion relates to a lesion’s functional connectivity with brain regions important for processing personal familiarity. Background: Capgras syndrome is a bizarre, fascinating disorder where a familiar person is perceived as an unfamiliar imposter. While right frontal lesions are known to impair belief monitoring and promote delusion formation, the neural mechanisms leading to the specific delusional content in Capgras syndrome remain controversial. Methods: First, we determined the neural correlates for personal familiarity by performing an ALE meta-analysis of fMRI studies in normal subjects. Next, we examined whether neuroanatomical lesions in patients with Capgras delusions (2 personal cases and 14 from the literature) were functionally connected with areas identified in our meta-analysis using a new technique called Lesion-Based Network Analysis. In this method, each individual lesion is used as a seed point to identify its functional connectivity network using a database of resting-state fMRI scans from normal subjects. Results: Our meta-analysis of 15 neuroimaging studies revealed that the left retrosplenial cortex is the region most consistently activated by personally familiar stimuli. In patients with Capgras delusion, 15/16 lesion locations (94%) were functionally anticorrelated with the left retrosplenial cortex, overlapping the area activated by personally familiar stimuli. Functional connectivity with the left retrosplenial cortex was specific to patients with Capgras syndrome compared with patients with other neurological syndromes. Conclusions: Patients with Capgras syndrome have focal lesions that are functionally connected with regions involved in personal familiarity. Our results provide a novel conceptual model to explain how one lesion causes the “two hits” that lead to a delusional disorder: a “destructive lesion” in the frontal lobe the allows for the pathological persistence of delusions and a “functional lesion” in a connected brain region that generates the delusion content.

Objective: To determine the clinical course, neuroanatomical localization, neuropsychological abnormalities, and delusional content in patients with delusional misidentification syndromes (DMS) occurring after focal neurological injuries. Background: Delusional Misidentification Syndromes (DMS) describe persistent beliefs of hyper- or hypo-familiarity for meaningful objects in one's environment. On the one hand, familiar persons or places can seem unfamiliar, perhaps even replaced by imposters; conversely, unfamiliar persons or places may seem familiar and in disguise. Despite growing recognition of DMS in the setting of focal neurological disease, a systematic evaluation of the clinical presentation, localization, and clinical outcomes in this disorder has been incomplete. Methods: We searched PubMed for all reported cases of DMS occurring in the setting of acute neurological injury through 2014. Results: Out of 507 papers identified, 61 cases with clinical and neuro-anatomical data met inclusion criteria. Delusions were recognized as hypo-familiar in 28 patients, hyper-familiar in 27 patients, and both hypo- and hyper-familiar in 6 patients. Recognition of the delusion after the time of injury was often delayed, typically up to 2 months. In most cases, the delusions spontaneously resolved or substantially improved over several months. Premorbid psychiatric disease, dementia, and advanced age were uncommon. Lesions were most frequently right-sided (90%) and frontal (63%). Cognitive impairments were common, including impaired memory (73%), executive dysfunction (52%), and visuospatial dysfunction (38%). Delusions were often not restricted to a particular category of objects, such as persons or places; 19 patients (29%) reported delusions across 2 or more categories. Conclusions: These findings provide a comprehensive analysis of the clinical course, localization, and delusional features of DMS, providing insights into the potential mechanisms of these interesting disorders.

Background: Inflammatory demyelinating disease (IDM) of the central nervous system includes Multiple sclerosis (MS), acute demyelinating encephalomyelitis (ADEM), and other less frequent entities. These illnesses can present with a broad range of symptoms, creating a diagnostic challenge for clinicians. Even more challenging are those who present with a psychiatric prodrome. Little is known about how psychiatric illness as a prodrome of white matter disease can affect time to diagnosis, treatment, and outcome. We review a case series presenting to neurology with primarily psychiatric symptoms and who were later found to have demyelinating illness, highlighting the challenges for providers. Case Series: Patients were seen in the inpatient and outpatient neurology department at a university tertiary care center. Neurological diagnoses include multiple sclerosis (MS), ADEM, probable MS, and undetermined white matter disease. Psychiatric diagnoses in these patients include bipolar disorder, depression, anxiety, and psychosis. In each case there was a delay to presentation to neurology, diagnosis, or treatment due the psychiatric prodrome. We reviewed the literature on psychiatric illness in demyelinating disease. Early presentation and treatment have been shown to correlate with improved outcome. But little is known about how psychiatric illness affects time to presentation, diagnosis, and treatment in this patient population. Conclusions: Psychiatric symptoms are common in IDM of the CNS, and may delay presentation to neurology, diagnosis, or treatment. The incidence and effects of a psychiatric prodrome in IDM is not well studied, and warrants further research. The possibility of demyelinating disease should be considered in atypical psychiatric presentations.

Background: Historically genetic testing has individualized treatment in the fields of immunology and oncology. Recently, several commercial genetic tests have become available to assess an individual's genotype for the major cytochrome p450 enzymes responsible for psychotropic drug metabolism, folate metabolism, serotonin transporter gene and the serotonin receptor gene. Objective: The purpose of this study was to monitor how clinicians utilize pharmacogenetic test results in an outpatient psychiatry clinic. Methods: After researching several commercially available genetic testing options, we established an account with a FDA approved company that had support from studies published in peer review journals. Clinic patients were considered for testing due to treatment resistant depression, a history of multiple failed medication trials, and/or sensitivity to medications. Data were collected over a 8 month period from November 2014 thru June 2015. Results: The clinic tested 29 patients for metabolism of psychotropics. Ages of patient ranged from 16–73 consisting of 21 women and 8 men. Chart review revealed that based on the genetic test the clinician altered the patient’s medication dosage ∼35% of the time, discontinued patient’s medication ∼15% of the time and started a new medication ∼38% of the time. Conclusions: Pharmacogenetic testing provides valuable information to the patient and clinician. Given the availability of testing and increased coverage by insurers, it is feasible to implement pharmacogenetic testing into clinical practice. Treatment outcomes may improve through genetic testing and should monitored by administering standardized questionnaires, such as a PHQ-9, at each patient visit.

Background: The LRRK2 gene is an associated risk factor for early onset Parkinson’s Disease and has been reported in association with familial Parkinson’s Disease. There is some genetic variation responsible for autosomal dominancy in the patient with familial Parkinson’s disease. Studies have shown more than 10% of the patients with Parkinson’s disease have one or more relatives with this disease. Early onset has gradual progression and can affect cognition at early age. Case: The patient is a 23 year old Asian American male, who was diagnosed with juvenile onset Parkinson’s Disease when he was 17 years old. Parkinson’s disease has affected his mental health; he has been diagnosed with depression as well as anxiety and has had two psychotic episodes while receiving anti-Parkinsonian medications. He is positive for the LRRK2 gene. His maternal grandmother had early onset Parkinson’s Disease at the age of 40 years. The patient is prescribed fluoxetine, lorazepam, and levodopa/carbidopa. He is status post Deep Brain Stimulation (DBS) placement, implanted at the age of 20 years. He presents with mild bradykinesia, bradylalia, dysphonia, dystonia, and dyskinesia. He is able to walk without assistance although at times has a slowed gait disturbance. Conclusion: This case illustrates the complexity of medical and psychiatric symptoms in patients with juvenile onset Parkinson’s disease. The etiology leading to the development of psychiatric disorders in this disorder, the role of medications, and prognosis for mental disorders with respect to neuropathology is an area requiring further exploration. While treatment options for this neuropsychiatric disorder include medications, neuromodulatory electrical treatments, and psychotherapy, therapeutic intervention is an area needing further development.

Background: Palinopsia or visual perseveration, is a rare visual disturbance in which images persist in the visual field after a visual stimuli has been removed.^1,2 It has been associated with substance intoxication or neurologic dysfunction.^1,2 We present a case of primary central nervous system vasculitis (PCNV) diagnosed by imaging and clinical history that presented with depression, confusion, and palinopsia. We believe this is the first documented case of of PCNV presenting with palinopsia. Case History: 46 y/o AA female with history of Human Immunodeficiency Virus (HIV) with a nondetectable viral load presented with increasing confusion, depressed mood and visual hallucinations over 2 weeks. She described visual perseveration consistent with palinopsia that resolved within 24 hours of admission. She was found to have occipital and parietal lacunar strokes and severe stenosis in her cerebral vasculature that was most consistent with PCNV. She received a prednisone and cyclophosphamide burst and had no further strokes. Case history, work up, and mechanism for palinopsia are discussed. Conclusions: Clinicians are frequently called to assess visual hallucinations and must remain vigilant for signs of potentially life threatening emergencies. Palinopsia can herald potentially devastating central nervous system disease and awareness of this symptom is critically important for clinicians.

1. Praveen-Kumar S, Rajesh A: Palinopsia without visual field defect: case report and minireview. Clin Neurol Neurosurg 2014; 125:207–209

2. Gersztenkorn D, Lee AG: Palinopsia revamped: a systematic review of the literature. Surv Ophthalmol 2015; 60:1–35

Background: Metronidazole induced encephalopathy is a rare complication of metronidazole that consists of encephalopathy, cerebellar dysfunction, and seizures. Metronidazole has high CSF bioavailability and is mainly metabolized in the liver. We illustrate a patient with end stage liver disease who presented with confusion initially thought to be from hepatic encephalopathy. However, neuropsychiatric symptoms of agitation, memory loss, and bizarre behavior prompted an alternative diagnosis based on characteristic MRI brain findings. Case History: A 49 year old woman with end stage liver disease presented with a 2 week history of confusion and agitation. Ammonia level was 80 and was placed on Lactulose and Rifaximin. She had fluctuations between lethargy, agitation, and confusion. She had orientation, learning, calculation, and memory problems. Right sided facial dyskinesias and bilateral appendicular ataxia were also observed. She also had a recent intraperitoneal abscess that was treated with a 6 week course of metronidazole totaling 43 g. EEG showed generalized slowing with no triphasic waves or seizures. MRI brain revealed T2/FLAIR hyperintensities involving the splenium of the corpus callosum, and bilateral dentate nuclei, midbrain, and basal ganglia, suggestive of metronidazole induced encephalopathy (MIE) [Figure 1.] Metronidazole discontinuation resulted in encephalopathy improvement several weeks later. Conclusions: MIE is a rare complication of metronidazole that clinicians should recognize, especially in patients with prolonged treatment and liver impairment. Common presentations include alterations of consciousness, cerebellar dysfunction, and seizures. MRI brain characteristically shows T2/FLAIR bilateral cerebellar dentate nuclei, brainstem, and splenium of the corpus callosum involvement. MIE is usually reversible after metronidazole discontinuation.

Background: The T-type voltage-gated Ca2+channels (T-VGCCs) are involved in the pathophysiology of epilepsy, pain and sleep. We found the mechanism underlying cognitive enhancement of a novel Alzheimer disease drug candidates, ST101 (Phase II in USA) and SAK3 (Ethyl-2’,3′-dyhydro-8-methyl-2’,4-dioxo-2-peperidinospiro[2-cyclopentene-1,3′-imidazo[1,2- a]-pyridine]-3-carboxylates) which improve the impaired memory observed in olfactory bulbectomized (OBX) mice by enhancing hippocampal acetylcholine (ACh) release via stimulation of T-VGCC. Objective: We investigated the effect of SAK3 on various isoforms of T-VGCCs and hippocampus-dependent memory. Methods: Neuro2A cells were transfected by T-VGCC α-subunit CACNA1G (Cav3.1), CACNA1H (Cav3.2), or CACNA1I (Cav3.3) with green fluorescent protein using lipofection. Results: The whole cell path-clamp recording indicated that all T-VGCC currents reach a peak at minus 40 mV. Both ST101 (100 p.m.) and SAK3 (100 p.m.) treatments rapidly enhanced Cav3.1 currents and SAK3-enhanced currents were greater than ST101-enhanced currents. SAK3 (100 p.m.) treatment also enhanced Cav3.3 T-VGCC currents but not Cav3.2 currents. Finally, SAK3 (0.1 mg/kg, p.o.) administration improved impaired memory-related behaviors seen in OBX mice, and the effects were blocked by preadministration of T-VGCC selective blocker NNC 55–0396 (12.5 mg/kg, i.p.). Cav3.1 T-VGCC was highly expressed in the cortex and hippocampus, suggesting that SAK3 improves memory deficits via stimulation of Cav3.1 T-VGCC. Conclusion: The novel cognitive enhancer SAK3 acting on T-VGCC can be a potential candidate of therapeutics for Alzheimer disease. This work is supported by Translational Research Network Project (AMED, Japan).

Background: Semantic dementia (SD) is a neurodegenerative condition characterized by loss of perceptual meaning. This loss of meaning is multimodal may extend to bodily symptoms. Objective: To investigate the hypothesis that somatic symptoms are often misinterpreted in SD. Methods: We performed a retrospective (1996–2014) cohort study of clinical data from the behavioral neurology program at the University of California Los Angeles. Fifty-three patients with SD were compared with 125 controls consisting of patients with Alzheimer disease (AD) of comparable impairment and age. A binary logistic regression model was used to control for age, gender, education and disease duration. Results: The prevalence of somatic misinterpretation in SD was significantly higher than the prevalence of somatic misinterpretation in AD (41.5% versus 11.2%) in a ratio of 3.7:1 (p<0.01). Observed symptoms included reduced or exaggerated responses to sensory stimuli, loss of recognition of internal sensations, loss of recognition of body parts, and Cotard syndrome. Conclusions: Semantic dementia is associated with somatic misinterpretations. These symptoms may result from the multimodal loss of meaning in semantic dementia resulting in loss of the meaning of body parts and misinterpreting ordinary bodily sensations. The misinterpretation of somatic symptoms in SD results in heightened distress and potentially unnecessary tests and offers offers clues to the potential source of somatic symptoms in other patients.

Background: sAPPβ, a protein involved in the initial phase of AD pathogenesis, has been suggested as a potential biomarker for AD dementia. Objective: The aim of the present study was to investigate the plasma sAPPβ concentrations in a predementia phase of AD, mainly in mild cognitive impairment (MCI) due to AD. Methods: 21 patients with MCI due to AD (MCI-AD) and 43 patients with AD dementia meeting the National Institute for Ageing-Alzheimer's Association (NIA-AA) criteria and with typical FDG PET findings for AD were included in the study. The study also included 24 elderly individuals with normal cerebrospinal fluid (CSF) biomarker profiles and without any neuropsychiatric disorders or subjective memory deficits. The study sample was recruited at the hospital of the Technische Universität München. sAPPβ plasma levels and Apolipoprotein E (APOE) genotypes were determined in all study subjects. SPSS v.21 was used for statistical analyses. Results: The statistical analyses were based on Kolmogorov-Smirnov-Test, analysis of variance, Bonferroni post hoc analysis, Kruskal Wallis test, Mann Whitney test and Chi-square test as appropriate. Plasma sAPPβ levels were significantly lower in patients with MCI-AD in comparison to that of controls (p=0.02), while they did not differ from that of patients with AD dementia (p=0.67). sAPPβ plasma levels were significantly lower in patients with dementia due to AD compared with controls (p<0.001). Conclusion: sAPPβ plasma levels are significantly lower in patients with MCI-AD than in controls suggesting the potential utility of sAPPβ in plasma as a biomarker candidate of predementia AD.

Background: Young- onset dementias often represent unusual etiologies. Symmetric abnormalities on brain MRI are easy to overlook, but their identification is a critical aid in dementia diagnosis. We present a case of young onset dementia associated with extrapyramidal signs and symmetric T2 hypointensities in the globi pallidi and substantiae nigrae. Case History: Over 11 months, a previously healthy 34 year-old Kuwaiti police officer gradually developed social withdrawal, drowsiness, irritability, and anxiety as well as a severe transcortical sensory aphasia and memory loss resulting in a MoCA score of 8/30. His physical exam revealed general hypereflexia with bilateral ankle clonus plus a slight resting tremor with bradykinesia and inability to change directions causing walking collisions. Brain MRI showed bilateral symmetric T2 and T1 hypointensities in the globi pallidi and substantiae nigrae with T2 hyperintense streaking of the medullary laminae separating the internal and external pallidal segments. Brain FDG-PET showed hypometabolism of all cortical lobes on the left with normal metabolism of the subcortical nuclei and right cortices. Whole exome sequencing revealed a p.T11M mutation in the C19orf12 gene consistent with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN), a form of Neurodegeneration with Brain Iron Accumulation (NBIA). Conclusion: This is the latest onset of MPAN reported; other cases with this mutation also had later onset, suggesting a genotype- phenotype correlation. This is the first brain FDG-PET reported in MPAN, and it demonstrates asymmetric cortical hypometabolism. The spectrum of MPAN and NBIA is wider than previously thought largely because of advances in imaging and genetics.

Background: Ornithine transcarbamylase (OTC) is an integral enzyme in urea synthesis. OTC deficiency is an X-linked disorder that results in accumulation of ammonia and other excitotoxins and can present with acute hyperammonemic encephalopathy and neonatal lethality. Chronic neuropsychiatric symptoms of adults with OTC deficiency have not been systematically described. We present two cases of OTC deficiency identified in adults with neuropsychiatric impairments outside of acute hyperammonemic encephalopathy. Case Histories: Case 1 is a 57 year old male who was diagnosed with OTC at age 48 following an episode of hyperammonemic encephalopathy. Imaging revealed enlarged ventricles, and cortical atrophy. He recovered, returned to full employment and was followed for mild depression and anxiety. By age 55, he began to have dietary compulsions, then mood fluctuations, followed by clear cognitive decline and progressive atrophy on imaging despite regular follow up for OTC and normal spot ammonia levels. Case 2 is a 53 year old female with a history of intellectual disability and epilepsy without diagnosed etiology who was diagnosed with OTC at age 52 during a prolonged hospitalization for hyperammonemic encephalopathy. Imaging demonstrated frontotemporal cortical atrophy. Neuropsychiatric symptoms included moderate intellectual disability, impulsivity, anxiety and irritability outside of the acute encephalopathy. Conclusion: OTC deficiency results in accumulation of ammonia and excitotoxins, and can result in episodes of hyperammonemic encephalopathy. Our cases indicate chronic or progressive neuropsychiatric symptoms and cerebral atrophy may also occur. Whether the etiology of these changes is from subclinical hyperammonemia or from another mechanism is unknown.

Background: “Content-specific” or “monothematic” delusions are fixed, false beliefs relating to a specific topic. These singularly focused delusions are distinct from the complex “polythematic” delusional systems of schizophrenia and can be striking in their presentation, often occurring in the absence of other thought disorder or perceptual abnormalities. Case History: The most frequently encountered subset of monothematic delusions are the delusional misidentification syndromes (DMS), in which individuals believe that specific people or places are something other than what they are. We present two cases of DMS: one demonstrating delusional hypoidentification of person (Capgras syndrome) with multiple sclerosis; and the second delusional hyperidentification of place (environmental Frégoli syndrome or reduplicative paramnesia) following thalamic and basal ganglia hemorrhage. Both are accompanied by computed tomography (CT) imaging demonstrating right hemisphere subcortical injury. DMS has been described in association with a variety of lesion locations and disease processes, with right prefrontal, temporal, parietal and limbic cortices and the subcortical circuits linking them most frequently implicated in neuroimaging and neuropsychological studies. While the precise neural basis of delusions has yet to be elucidated, the “two-factor” model has offered some insights: here, a primary neuropsychiatric deficit (1) gives rise to an unusual experience that is then (2) inappropriately accepted or incorrectly interpreted due to a second impairment in self-monitoring and metacognition. Conclusions: Delusional phenomena can contribute to complex presentations in neuropsychiatric illness across a spectrum of severity. The two-factor approach may offer a window through which to examine a wide range of multifaceted neuropsychiatric syndromes.

Background: Neuropsychiatric differential diagnosis of nonverbal and minimally responsive presentations includes, but is not limited to, catatonia of neurologic or psychiatric origin, hypokinetic delirium, major depression, and akinetic mutism (AKM). AKM is characterized by a lack of verbal and motor output and preserved alertness in the absence of demonstrable disturbance of corticospinal or language pathways. AKM can be caused by tumors, trauma, infection, anoxia, and stroke and is typically associated with lesions involving the frontal lobe, thalamus, mesencephalon and periventricular structures. Subcortical lesions driving AKM are thought to disrupt frontal-subcortical loops that subserve motivated behavior. Case History: We present a case of AKM after resection of a pituitary macroadenoma. The patient had been psychiatrically hospitalized 2 weeks prior to admission for a diagnosis of depression. Mention of catatonic features was noted. Bupropion had been initiated. Marked psychomotor slowing was noted on postoperative day (POD) #5. Diagnoses of hypokinetic delirium, depression or tumor related catatonia, and AKM were initially considered. A trial of lorazepam was without benefit. Postoperative imaging was notable for increased edema and significant residual tumor abutting ventral striatal structures. A course of steroids was initiated to address diagnostic possibilities of tumor / surgery related edema effects on striatal motor-relevant pathways and HPA axis dysfunction as causes of AKM – and resulted in prompt and significant improvement in psychomotor slowing and mutism. Conclusions: This case adds to the literature of lesion location and AKM – and suggests a role for steroids in the treatment of AKM when edema is thought to be playing a role.

Introduction: ECT is the treatment of choice for catatonia. We describe a unique case of a patient with no prior personal or family history of bipolar disorder whose catatonia was successfully treated with ECT but became manic after ECT. Case: 20-year-old African-American female patient presented to the hospital for vaginal bleeding due to missed abortion but was found to be confused with disorganized thinking and auditory hallucinations. As per the patient's mother, her psychiatric symptoms started after the patient had the abortion. She also progressed to catatonia, which did not respond to lorazepam. But she had a dramatic improvement in her catatonia with ECT. However she remained psychotic and eventually became manic with euphoric mood, pacing, inability to sleep, hypertalkativeness, which did not improve but rather seemed to worsen with ECT. ECT was discontinued after which the patient became more depressed yet remained psychotic despite increasing her antipsychotic medications. The patient was then started on lithium and within few days, the patient was back to her baseline with resolution of mania and psychosis. Conclusion: ECT is the treatment of choice for catatonia. It is also indicated for unipolar depression and bipolar disorder. However few case reports describe the possibility of ECT- induced mania. Hence it is important to keep in mind that even though ECT is a potential treatment for bipolar disorder, it may also induce mania, even in patients with no prior history of bipolar disorder. In such cases discontinuation of ECT and initiation of moods stabilizers are recommended.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is indicated for the treatment of depression and is being explored as a treatment for other neuropsychiatric conditions like migraines. We present a case of a patient who showed significant improved of both refractory migraines and depression with rTMS. Case: A 67 year old Caucasian female patient was referred by her neurologist for evaluation for rTMS for intractable migraines. She described it as a pulsating headache usually on the left side accompanied by nausea and at times vomiting. At times she experiences an aura in the form of blinking lights. Triggers for the migraine include strong perfume, heat, sunlight, as well as intense emotions including laughter or crying. Her neurologist had tried multiple medications for her migraines which remained refractory. She reported that her migraines had significantly affected her functionality. Besides, she was complained of worsening depressive symptoms with depressed mood, suicidal ideation, decreased appetite, difficulty concentrating and anhedonia. We treated her with a 6-week course of rTMS, after which she reported improvement in both her depression and her refractory migraines. Conclusion: rTMS has both diagnostic and therapeutic applications for migraines. rTMS is being studied for both treatment and prophylaxis of migraines. The positive outcome in our patient who showed improvement in both her intractable migraines (which had failed multiple drugs) as well as depression with one mode of therapy–rTMS–is encouraging. Further trials would be appropriate to establish its safety and efficacy of rTMS for neuropsychiatric conditions.

Background: Literature is limited regarding the impact of VZV encephalitis to the developing blood brain barrier (BBB). This proposed defect increases potential external influence on the brain. Hormonally induced psychosis is uncommon, but may be more prevalent in individuals with BBB damage. Case History: Brockington has written most extensively on the topic of premenstrual psychosis and others advise various management strategies. The etiology remains unclear and is thought to be multifaceted with emphasis in the literature on the neuroendocrine axis, the ovulatory cycle hormone variation and interactions with catecholamine neurotransmitter system. However, we were unable to find data suggesting a predisposition to premenstrual psychosis secondary to damaged integrity of the BBB. We present a case of a 25-year-old Caucasian female with a past history of Intellectual Disability secondary to VZV encephalitis and psychosis with onset of menstruation. Her presentation was complicated with questionable epileptiform discharge, antiepileptic medications, urinary tract infections, catatonia and delirium. However, prior to menstruation the patient experienced abrupt change from baseline; symptoms of internal preoccupation, paranoia, and insomnia remitted with completion of menstruation. It was the hypothesized concept that damage to the BBB increased susceptibility to sex steroid fluctuations, resulting in a phenotypical presentation of premenstrual psychosis. Management strategies for her care thus included continuous birth control, cycle specific dosing of Olanzapine, and prophylactic Bactrim. Conclusion: Damage to the BBB may increase susceptibility to premenstrual psychotic symptoms. A better understanding of this physiology could improve diagnosis, treatment and outcome for patients with underlying BBB damage.

Background: Ataxia-telangiectasia (AT) is a neurodegenerative cerebellar disease of childhood. Hoche et al. (2014) reported cognitive and behavioral symptoms in AT, but the neuropsychiatric impact of cerebellar degeneration has not been addressed. We hypothesized that cerebellar pathology in AT would disrupt the universal cerebellar transform producing dysmetria of thought, and manifest as the CCAS (Schmahmann and Sherman, 1998; Levisohn et al., 2000) / Schmahmann’s syndrome (Manto and Mariën, 2015). Objective: To investigate the effect of cerebellar and cerebrocerebellar pathology on the developmental neurocognitive profile in children with AT. Methods: Twenty-one AT patients were grouped into early-stage cerebellar (AT-I) versus late-stage cerebrocerebellar disease (AT-II) and examined for CCAS impairments in executive, linguistic, visual-spatial, and affective/social-cognitive domains. Scores were converted to z-scores, and compared with healthy controls and standard norms. <1 S.D. from the mean was considered normal. Results: AT-I patient z-scores were low average to impaired on CCAS domains. Full-scale IQ: –0.68, executive function: –1.44, working memory: –0.17, verbal comprehension: –0.24, visual-spatial: –0.90, (visual-motor integration, VMI): –1.07 (motor-free). AT-II patients showed more severe deficits: full-scale IQ: –1.08, attention:-0.97, executive function: –1.12, working memory: –1.26, language: –0.36 (expressive), 0.29 (receptive), verbal comprehension: –0.34, visual-spatial: –2.36, (VMI): –1.04 (motor-free). Parent questionnaires indicated difficulties with affect regulation, social skills, attentional control, planning, and sequencing. Tests of social cognition were impaired including recognition of positive emotions from faces (p<0.05) and theory of mind tasks. Conclusion: Children with AT exhibit the CCAS which evolves along with age and disease severity. These results provide empirical support for a universal cerebellar transform enabling cognitive regulation in children and adults.

Background: Traumatic Brain Injury (TBI), the “signature injury” of the wars in the Middle East, is often comorbid with chronic pain, and posttraumatic stress disorder (PTSD). There is still much to be learned regarding the neuroanatomy, neurophysiology, and clinical assessment/treatment of this triad. Very few teaching materials are available for the neuropsychiatric sequelae of war-related blast injuries. Objectives: To create and disseminate teaching materials that translate complex concepts into clinically useful knowledge for betterment of patients; To create integrated materials and guided learning experiences that also promote usability of knowledge. Methods: New clinical and research findings relevant to these conditions were reviewed, synthesized, and summarized into graphic rich original teaching materials in which color carries a significant portion of the information, allowing large volumes of new information to be presented without overwhelming the learner. Results: Evaluations from parts I - IV of this series (2009, 2012, 2014, 2015), were very positive and indicated the need for more integrated materials of this type. Incorporating the latest work in war-related injuries, Part V will further facilitate the translation of “textbook to bedside application”. The connections between functional neuroanatomy, neurophysiology, and clinical presentation will be elicited, allowing learners a deeper interest in individual aspects of each patient, and enhance appreciation of comorbid pathologies and prognosis. Conclusion: These newly revised tools support guiding learners through the intricacies of this complicated field, promoting development of active, integrated knowledge required for the clinical practice of neuropsychiatry as it relates to war-related TBI.

Background: Mania due to traumatic brain injury, or posttraumatic mania, is a relatively infrequent, brief, and functionally limiting consequence of TBI. Optimal treatments for posttraumatic mania remain uncertain, although two prior reports (comprising three cases) described its resolution with quetiapine. We present a fourth case of quetiapine-responsive posttraumatic mania. Case History: A 52-year old, right-handed, previously psychiatrically healthy, woman was admitted to acute rehabilitation two months after a severe traumatic brain injury. During the four weeks prior to admission, she developed persistently irritable mood, insomnia, pressured speech, inflated self-esteem, hyperactivity, and distractibility. Her examination also revealed Wernicke aphasia, and staff reported agitation and aggression (Agitated Behavioral Scale [ABS] score proximate to consultation=41). Computed tomographic imaging showed damage to the bilateral anterolateral temporal (left greater than right) and bilateral ventromedial frontal (right greater than left) cortices and white matter. Quetiapine 75 mg was added to her medication regimen and titrated over one week to 300 mg daily, after which her mood, sleep, and behavioral symptoms improved (ABS score declined 40%). Concurrently, her aphasia evolved from Wernicke to anomic and she tolerated treatment well. Conclusions: The present case replicates prior reports of quetiapine-responsive posttraumatic mania. The relative contributions of quetiapine, alone or in combination with her other medications, and spontaneous recovery of the patient’s posttraumatic mania remain uncertain. However, the rapidity of symptomatic response suggests that quetiapine was the predominant contributor to its resolution. This and similar prior observations support quetiapine as a treatment option for posttraumatic mania.

Background: Delusional misidentification syndromes are uncommon and occur predominantly in persons with acquired brain injuries and neurodegenerative disorders. To our knowledge, the sensation of a phantom piece of clothing has not been reported in the literature. We present a patient with episodic Capgras syndrome and the persistent hallucination of wearing a vest following a traumatic brain injury (TBI). Case History: The patient is a 31-year-old left-handed man who experienced a severe TBI. On exam, he exhibited left hemineglect and left hemiparesis. He experienced Capgras delusion, in which he believed his wife was an imposter. The delusion only occurred when she was present in his room, not when they talked on the phone, and was typically triggered when his wife was in his neglected hemispace. He additionally reported the constant, hallucinated, sensation of wearing a vest. Computed tomography revealed injury to bilateral (predominantly right-sided) frontal polar, orbitofrontal, and anterior temporal structures and to right dorsolateral and temporoparietal structures. Conclusion: This patient experienced Capgras delusion in the visual but not auditory modality following TBI. Our findings support the hypothesis that disruption of right-hemispheric pathways connecting facial recognition and limbic-paralimbic areas can cause Capgras delusions. Right hemisphere damage also underlies disturbances of body representation. Coupled with impaired insight arising from lesions to these and frontopolar areas, disorders of body representation may extend to false perceptions of body accoutrements such as clothing, in addition to disturbances in the perception of the body itself.

Background: Functional Neurological Symptom Disorder (FND) patients present as a heterogeneous group. Research suggests two general patterns of emotional under-regulation and over-regulation. Alexithymia, dissociation, and somatization are common. Without clear treatment guidelines, providers are reluctant to treat FND patients. Prior studies on group Dialectical Behavioral Therapy (DBT) and Psychodynamic Psychotherapy (PP) in FND have been promising, but more research is needed to tailor effective treatments. Objectives: • Measure psychological characteristics and treatment outcomes in FND patients receiving group PP versus DBT. • Hypothesis: Participants in both groups will improve with regards to symptom frequency and affective scores. Emotionally over-regulated psychological profiles will respond better to PP emphasizing emotional expression. Emotionally under-regulated profiles will respond better to DBT targeting emotional regulation. Methods: 12 subjects enrolled (with continued enrollment). Measures collected include symptom frequency, Toronto Alexithymia Scale, Dissociative Experiences Scale (DES), Difficulties in Emotional Regulation Scale, and questionnaires for somatoform symptoms (SDQ-20), attachment (ASQ), trauma (ACE), depression and anxiety. Results: Baseline descriptive results tended to cluster at opposite extremes. For example, DES participant scores had a bimodal distribution, with 50% falling in a range suggestive of dissociative disorders (DES>35). 33% of the sample categorized as “low-alexithymia” and 17% as “high-alexithymia.” We are currently in week 16 of 32. Based on analysis of change in a mixed effect model, postintervention results will be discussed with respect to psychological profiles. Conclusion: This pilot study examines psychological characteristics and treatment outcomes in DBT and PP for FND. Further research on psychological characterization may inform psychotherapeutic interventions.

Background: Poststroke acute confusional states can present with or without other neurological signs and complicate the diagnostic, evaluation, and management process. The broadened differential which any case of delirium represents and the heightened risk associated with this condition are challenges to consider clinically. This case describes cognitive deficits, agitation and fluctuating sensorium arising for the first time for a patient after experiencing stroke. The condition evolved over a one week period requiring inpatient psychiatric evaluation and management in an elderly male previously known to have atrial fibrillation. Notable in this patient’s presentation is the delirium, the challenges to his proper diagnosis and treatment, and the variety of neuropsychiatric interventions considered. Case: The patient is a 71 year old single white male admitted after he presented with agitation and confusion one week after he was noted to have signs of a right hemisphere stroke. Neuroimaging revealed a right sided temporoparietal lesion involving the right MCA territory at an outlying hospital. The hospital course was notable for his behavioral disturbance and delirium after transfer. Repeat neuroimaging failed to reveal any further changes. After evaluation for other causes for delirium, the patient was treated with low dose olanzapine at bedtime which resulted in improvement in sleep, behavior, and confusion. Despite this improvement in behavioral parameters, the patient expired. Conclusion: Poststroke delirium has been described in a variety cases with differently located discrete lesions. This case illustrates the complexity of presentation and management.

Background: Catatonia is a complex clinical presentation associated with variety of psychiatric and neurological illnesses. Understanding the basics presentation and mechanism of catatonia can help clinicians identify and formulate effective diagnostic and treatment plan. Case History: Ms. D is a 68 years old female with PPH of bipolar affective disorder and PMH of ovarian cancer s/p resection, intestinal obstruction (intestinal adhesion) was readmitted to the hospital for intestinal obstruction. Patient’s bipolar affective disorder was stable on Geodon. Psychiatry was consulted after surgery (intestinal obstruction) for management of AMS. Patient was diagnosed with metabolic encephalopathy and managed appropriately. Psychiatry was reconsulted after 2 weeks for new onset confusion and inability to respond. Patient’s after re-evaluation was found to be catatonic. All antipsychotics were discontinued and trial of Ativan was offered. Motor signs (posturing, rigidity, waxy flexibility) of catatonia responded well to Ativan but patient remained cognitively unresponsive. On neurological examination pupils were anisocoric. CT revealed hydrocephalus and possible mass around cerebral vermis. Provisional diagnosis of fourth ventricular ependymoma was made after MRI. Mass was resected and biopsy of mass came back positive for CNS lymphoma. Patient’s catatonic features improved post surgically as hydrocephalus was corrected. Patient, however, developed intracerebral bleeding later on was transferred for palliative care given poor prognosis. Conclusions: Pathophysiology of catatonia, although not fully understood, involves interaction of various neurochemical systems (glutamate, dopamine and GABA). Many structures in brain, when damaged, can affect the neuro-circuitry of basal ganglia giving rise to catatonia features.

Background: Apraxia of speech and dysarthria are two major components of motor speech disorder in speech production. Recently, progressive apraxia of speech has attracted much attention in the diagnosis of progressive nonfluent aphasia. However, only a few cases of progressive dysarthria have been reported so far. Case History: A 60-year-old right-handed man had noticed speech and swallowing difficulties 3 years previously. Neurological examinations showed no abnormality other than a slight limitation of palatal movement. He had hypernasality and a slow rate of speech with distorted consonants and vowels, but he did not show apraxia of speech nor aphasia. Neuropsychological examinations showed no abnormality in his cognitive functions including memory and frontal lobe functions. He did not show any personality changes and behavioral abnormalities from initial stage of the disease. Magnetic resonance imaging showed cortical atrophy in the temporal lobes bilaterally. IMP single photon emission computed tomography showed decreased blood flow and activity in medial frontal lobe, predominatly on the left side. Thus, he was clinically diagnosed with FTLD. After one year his dysathria became aggravated. He became mute and started writing message to communicate with. Conclusion: After 3 years from the onset of pseudobulbar paretic dysarthria and dysphagia, only dysarthria advanced more rapidly than dysphagia. This case is a pure case of progressive dysarthria which could be classified as a variant of FTLD.

Background: The emergence of mania after a stroke is thought to comprise fewer than 1% of strokes, in contrast to up to 40% of poststroke patients who develop major depression. Poststroke mania is rare, has not been well characterized in the literature, and treatment is currently not well defined. Our case portrays numerous components of this seldom described condition and illustrates the need to identify more definitive treatment recommendations. Case History: Our patient is a 68 year old male with no personal or family psychiatric history who developed AMS after coronary artery bypass surgery. An MRI revealed that he suffered an ischemic stroke affecting both hemispheres, most significantly the right parietal lobe. The following month he had two car accidents the same day while driving to the airport for a flight for which he had no ticket, and presented to our ED acutely manic and psychotic, with CT yielding evidence of possible petechial parietal bleed. His cardiac history and paranoia limited our treatment options. In a review of 49 cases of poststroke mania, only 2 of 49 patients presented with nine out of nine symptoms of mania measured. Our patient manifested all nine, in addition to left hemineglect. He was treated successfully with aripiprazole. Conclusions: While poststroke mania occurs in a small minority of patients, it is a potentially dangerous and debilitating condition, which warrants timely recognition and treatment. To our knowledge, this is the first case to describe the benefits of aripiprazole for treatment of poststroke mania.

Background: Young athletes who have sustained sports-related concussion(s) may consider retirement from sports based on their own volition or as recommended by the medical community. Retirement from sport postconcussion is a controversial topic, and the decision to retire is often a complicated one based upon medical, social and psychological factors. For the young athlete, retirement from sport can pose several psychosocial challenges that may complicate postconcussive neuropsychiatric symptoms. Neuropsychiatry is the medical specialty best suited to treat these patients who are often discharged from the care of other medical specialists, yet still in need of support and treatment postretirement. The clinical approach to the retired young athlete requires attention not only to their neuropsychiatric symptoms but also to the presence/absence of support systems while also considering the influence of any premorbid psychiatric or psychosocial issues. Unique circumstances or situations may arise for the young retired athlete, including legal, social, and school-related issues that stem from their original commitment to athletics causing change. There is a paucity of information available when treating these subpopulations that have overlapping needs: retired athletes, concussed individuals, and young men and women. Case History: Few cases exist in the literature to date on the neuropsychiatric sequelae for retired young athletes postconcussion. Here we present two relevant cases and the unique challenges they face in rehabilitation and recovery. Conclusion: A myriad of neuropsychiatric issues can be considered unique to the subpopulation of young athletes who retire from their chosen sports. Clinical considerations and future research in this area are highlighted.

Background: Vanishing White Matter Disease (VWMD) is a leukodystrophy that occurs with dysfunction of eukaryotic initiation factor-2B (eIF2B). The authors will present a case of a patient with homozygous missense mutations of exon 13 of subunit 5 of eIF2B who presented with intractable psychosis and aggression. Case History: Patient is a 23-year-old female with a history of complex partial seizures and a previous diagnosis of schizoaffective disorder who was admitted for psychosis. On presentation, patient was irritable, neglected hygiene and was episodically aggressive. She was observed to talk to self as though attending to hallucinated voices, posing questions to herself and answering them aloud. Patient was trialed on multiple antipsychotics and a course of ECT—all without benefit. MRI Brain showed confluent white matter disease with sparing of U fibers. Extensive blood, CSF, urine testing was negative, as was work-up for the classic inherited leukodystrophies. Testing for CARASIL and CADASIL was negative. Testing for VWMD demonstrated homozygous missense mutations in EIF2B5. Deletion/duplication analysis of EIF2B5 was negative for deletion or duplication. Discussion: Classically, VWMD manifests in early childhood with ataxia and cerebellar tremor leading to early demise. However, milder phenotypic variants with later onset and protracted course, as in our case, have been described. VWMD is caused by mutations in any of the genes that encode the five subunits of eIF2B. Our patient was found to be homozygous for variant p.Ile587Val of eIF2B5. This particular residue change has, heretofore, not been described in association with vanishing white mater leukoencephalopathy.

Background: Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by decline in higher visual function and focal atrophy of the parieto-occipital cortices. The authors present here a case of PCA. Diagnosis was aided using a validated in vivo method to map myelin content. To the authors’ knowledge, this study represents the first use of myelin mapping toward diagnosis of PCA. Case History: Patient is a 57-year-old female with a diagnosis of early onset Alzheimer’s disease who presented with depressed mood and nonspecific visual complaints. On presentation, patient endorsed palinopsia, dysmegalopsia and room tilt illusion. Exam disclosed Gerstmann’s syndrome and simultanagnosia without optic ataxia and/or oculomotor apraxia. MRI Brain from one year prior showed focal occipital atrophy without mesiotemporal atrophy. CSF was suggestive of Alzheimer’s disease pathology; however, genetic testing for APP and presenilin 1 and 2 was negative. Brain SPECT showed bilaterally decreased posterior cortical perfusion, consistent with PCA. Analysis of myelin content was performed by calculating a T1-weighted/T2-weighted ratio image as shown by Glasser and Van Essen, 2011. Discussion: The phenotypic and histopathologic heterogeneity of PCA results in underdiagnosis. Furthermore, consequent to PCA’s progressive nature, patients go on to develop a global dementia that is clinically and radiologically indistinguishable from typical Alzheimer’s disease. Localization of white matter atrophy to the ventral and dorsal visual pathways using DTI can be revealing but challenging to analyze. Myelin mapping represents a potential alternative. In our patient, T1w/T2 ratio analysis demonstrated posteriorly localized white matter atrophy, particularly of the ventral visual pathways.

Background: Catatonia is frequently under-diagnosed. Few studies have analyzed the characteristics of nondiagnosed catatonia in the general hospital. Objectives: To detect probable cases of nondiagnosed catatonia in a general hospital and compare them to diagnosed cases in the same time range. Also, to determine clinical characteristics related to catatonia not being diagnosed. Methods: A retrospective chart review was conducted of all inpatients at the University of Chicago between January 2011 and December 2013. The words “catatonic,” “catatonia” or the presence of three or more keywords describing catatonic signs were used to identify 1235 cases for review. Catatonia was diagnosed using DSM-5 criteria and Bush Francis Catatonia Rating Scale screening tool, retrospectively. Results: 97 cases met criteria for catatonia and had not been diagnosed, whereas 49 previously reported cases had a documented diagnosis of catatonia. Compared with diagnosed cases, nondiagnosed cases had significantly more catatonia due to medical conditions (82/97 versus 29/49 p<0.05), were more often evaluated by neurology service (82/97 versus 20/49, p<0.05), less often evaluated by psychiatry service (36/97 versus 44/49, p<0.05), and were less likely to receive lorazepam during the episode (14/97 versus 26/49, p<0.05). Comparing those with catatonia due to medical conditions, nondiagnosed cases had higher length of hospital stay (23.2 versus 14.5 days, p<0.05). Conclusions: A significant proportion of cases with catatonia in the general hospital are nondiagnosed and under-treated. This highlights a need for educational strategies to increase clinicians’ awareness of catatonia. Psychiatric consultation may improve recognition and management of catatonia in the general hospital.

Background: The mimic octopus is capable of impersonating other animals or blending in with their environment to intimidate or evade predators. Similarly, patients with frontotemporal dementia (FTD) are frequently misdiagnosed with primary psychiatric diagnosis due to failure to recognize clinical symptoms in the absence of diagnostic biomarkers. Delayed diagnosis may negatively impact management and intervention. Case History: A 53 year old married Caucasian female presented to outpatient psychiatry clinic as a referral from cardiology after multiple medical admissions for chest pain with negative work-up including cardiac catheterization. She reported a one and a half year history of ideas of reference, auditory and visual hallucinations, excessive involvement in pleasurable activities without thought for consequences. She was diagnosed with undifferentiated schizophrenia and started on antipsychotics. These were ineffective, and she was eventually placed on clozapine. Three years later, donepezil was initiated for noted decline in cognitive functioning. Eight years later, neurology was consulted for dementia and patient was diagnosed with behavioral variant FTD. In addition, she was found to have amyotrophic lateral sclerosis after electromyography demonstrated demyelinating motor neuropathy. Conclusions: The development of neuropsychiatric symptoms in FTD can be misdiagnosed as negative symptoms of schizophrenia. Psychosis is rare in FTD, as is comorbid FTD and ALS. In an atypical presentation of psychosis, the differential diagnosis including secondary to generalized medical condition and secondary to medication or substance use must be considered. Other features such as family history, response to medication, and age at onset can help predict outcome.

Background: Bing-Neel Syndrome is the extremely rare central nervous system involvement of Waldenstrom macroglobulinemia. Case reports and series have documented visual changes and delirium related to Bing-Neel, though have not documented isolated visual hallucinations. Case History: A fifty-three year old African-American man with past history of lymphoma (treated in outside hospital three years prior) presented with partial seizures and visual changes. Lumbar puncture demonstrated CNS involvement of lymphoma, and ophthalmology consultation team noted optic neuritis. MRI was performed and was within normal limits except subtle hemosiderin deposition in left occipital lobe. During treatment and related complications (including GI bleed due to steroids, R frontal Ommaya Reservoir placement, and worsening visual acuity) he became encephalopathic, with fluctuating level of consciousness, visual hallucinations of snakes, and delusions, which quickly resolved with risperidone. After resolution of delirium, he developed elementary hallucinations of “lines, plus and minus signs” which continued in clear consciousness until gradually resolving over time. He was continued on low dose risperidone, with gradual down-titration and discontinuation without return of hallucinations. A discussion of the potential pathophysiology of his visual hallucinations, including relation to sensory changes and attentional networks, will be included. Conclusions: This case report documents a rare focal finding in a patient with Bing-Neel syndrome, as well as demonstrating the clinical relevance of understanding attentional and visual networks.

Background: In 1922, Lhermitte described a patient with pontine localizing symptoms accompanied by visual hallucinations, which became known as peduncular hallucinosis. Case History: This is a case of a man with a history of atrial fibrillation and prior aortic valve replacement for aortic stenosis, hyperlipidemia, severe obstructive sleep apnea, without visual impairment or psychiatric history who presented to the emergency department during an episode of unresponsiveness. MRI/MRA showed no acute stroke. During the hospital admission that followed he was found to have a complete heart-block which required the placement of a pacemaker. He described multimodal hallucinations with paranoia, seeing assassins targeting him. He described the events as being like dreams. He also had loss of muscle tone. EEG during an event showed mainly sleep spindles. He developed a mild right 3rd cranial nerve palsy. An extensive workup for infectious, inflammatory, autoimmune or neoencephalitic etiologies was negative and there was no Parkinsonism. The events have continued to occur over the following 18 months, and have required two subsequent psychiatric hospitalizations. Conclusions: The combination of complex visual hallucinations and delusions could suggest Dementia with Lewy Bodies, though clinical history is more consistent with a vascular etiology localizing to the midbrain. This, along with the predominant sleep-spindling on EEG seen during the episodes suggest that peduncular hallucinosis can be a narcolepsy-like parasomnia rather than a cortical release phenomenon.

Background: The new DSM-5 diagnosis of Disruptive Mood Dysregulation Disorder (DMDD) has sparse research available exploring medical management of the hallmark symptoms of chronic irritability and severe temper outbursts that occur, on average, three or more times per week. Several recently published studies resultant from applying the official diagnostic criteria to large community-based populations indicate 3 month prevalence rates of 3.3% to 8.2% with poor long-term functional prognosis. Objective: The current study explores the feasibility of managing DMDD symptoms with a unique medication protocol consisting of anticonvulsant and dopaminergic medications, and without the use of antipsychotic medications. Methods: Subjects were 91 chronically irritable and explosive juveniles (52 male, 39 female: ages 6–17) with previous residential treatment for primary diagnoses of Bipolar, or other Mood Disorders, who met full criteria for DMDD upon retrospective chart review. All were discharged on oxcarbazepine and amantadine HCl and no antipsychotic medication. Outpatient physicians were requested to be compliant with the treatment protocol, but some were noncompliant and added or substituted antipsychotic medication. Results: The percent of rehospitalization at 6 months postdischarge were calculated separately for those whose aftercare physicians were, or were not fully compliant with the protocol. For the fully compliant, 8% (5 of 64) required rehospitalization. For those noncompliant, 26% (7 of 27) required rehospitalization. Using Chi Square analysis, there was a significant relationship between rehospitalization rates and compliance (Chi Square, two tailed with Yates=3.975. p<0.05; Phi=0.24). Conclusion: The data suggest that this protocol provides significantly positive outcomes for DMDD.

Background: Idiopathic late onset tic disorders–particularly Tourette Syndrome–are infrequently reported. In most cases, a personal and/or family history of childhood tic disorder is present. Here we report a case of late onset Tourette-like Syndrome with no childhood history of tic disorder. A possible link to mercury toxicity is suspected. Case History: The patient is a 55 year-old male whose symptoms emerged at age 50, beginning with paresthesia in the neck and face followed by headache, distal leg shock-like sensation, coprolalia, crescent-like momentary visual field loss, and motor tics triggered by auditory and visual stimuli. His family and personal history are unremarkable for any former tic disorder. No psychological stressors were identified. The patient formerly worked as a printing technician and was chronically exposed to film removers and printing ink. He stopped working in 2011. Neurological and cognitive examinations revealed a MOCA of 27/30, limb and vocal tics, phonemic fluency of 20 and semantic fluency of 26. Brain MRI, EEG, basic metabolic panel, liver enzymes, lipid profile, CBC, heavy metal and drug urine screen were all normal except for elevated serum mercury (8.5mcg/L). 24h urine mercury and hair sample results are pending. Conclusions: This is a rare case of late onset Tourette-like Syndrome accompanied by paresthesia, headache and momentary peripheral vision loss. Though mercury toxicity can cause some of these symptoms, the presence of vocal tics makes this an interesting and atypical case.

Background: The constellation of symptoms described in patients with nonconvulsive status epilepticus is extensive. Mental status disorder might be part of the presentation of NCSE. Elderly patients with confussional state need to be assessed in order to make an accurate diagnosis of other uncommon pathologies that might mimic neurocognitive disorders. Case History: A 65-year old woman with longstanding type 2 Diabetes arrived to the emergency unit with ten-day history of sudden onset of bradylalia and bradypsychia, difficulty in naming and refusal to eat. Upon admission she was mute, maintaining the same posture for long periods of time, with repetitive behavior such as wearing on/off glasses and opening-closing fists. She also presented echolalia and echopraxia. Further neurological examination showed paratonia, glabellar, snout, and palmomental reflexes with no other abnormal findings. Catatonia was diagnosed. Bush Francis Catatonia Rating Scale score was 6/15; the patient was treated with oral lorazepam 2 mg tid. Slight improvement on withdrawal symptoms was observed. Blood tests, thyroid function, lumbar puncture and CT scan were normal. On further evaluation an electroencephalogram (EEG) revealed triphasic waves suggesting an ictal pattern, nonconvulsive status epilepticus was diagnosed, upon administration of benzodiazepines triphasic waves disappeared. Conclusion: We report the case of an uncommon disease presenting with neuropsychiatric features such as catatonia. EEG is a useful tool in the clinical assessment of the elderly with acute onset of neuropsychiatric symptoms, but clinical suspicion might be the key to diagnosis. NCSE must be considered in the differential diagnosis of mental status disorders.

Objective: Evaluate the association of frontal release signs (FRS) with cognitive decline in subjects with intact cognition (CI), mild cognitive impairment (MCI), and dementia. Background: FRS are primitive reflexes that regress with brain maturation and reappear in the setting of brain injury or neurodegeneration. Their diagnostic utility in the setting of predementia cognitive decline is poorly understood. Design/Methods: We examined the prevalence and progression of FRS over 2,545 discrete annual visits in 689 subjects with CI, MCI, and dementia. Independent variables included diagnostic category and the absence or presence of FRS (≥2 positive). Results: Baseline FRS prevalence was 7.5% in CI, 28.6% in MCI, and 34.5% in demented subjects. FRS were associated with age (p<0.0001) and increased education (p=0.001) in CI subjects. FRS+increased the probability of transition at the next visit: 8.6% CI to MCI, compared with 4.4% FRS- subjects (p=0.0079); 26.9% MCI to dementia compared with 16.5% FRS- subjects (p=0.10). Linear mixed model regression analyses demonstrated an association of FRS+with significantly poorer cognitive test scores on Digits Forward (trials) (p=0.0022), for CI; Digits Backward (trials) (p=0.008), Digits Backward (length) (p=0.0362), and Trail Making Test A (p=0.0008) for MCI. Demented patients with FRS did not differ from those without. Conclusions/Relevance: FRS may have diagnostic utility in early in cognitive decline. FRS should be included in the evaluation of persons at risk for the cognitive decline or development of a degenerative dementia.

Background: Despite thousands of publications, “Consciousness” remains conceptually unclear, varying between specialties and even conceptualized differently within disciplines (e.g. Neuropsychiatry). Consequently, Neppe (2014) proposed four theoretical separate “axes” of “EPIC Consciousness”, each with subclassifications:

Questions / Hypotheses: This theoretical EPIC Consciousness classification requires empirical Neuropsychiatric validation. Is this four-pronged empirically based classification:

Clinical Reports: Clinical populations: Certain examples of major clinical neurological plus psychiatric diagnoses were examined: Movement disorders; Seizures; Attention deficit; Delirium; Dissociative; Headaches; Chronic brain syndromes; Systemic disorders; Temporolimbic dysfunctions. Subjects: Consenting neuropsychiatric patients at PNI with the above primary diagnoses. Evaluation methods applied: EPIC Classification; Mental status; Diagnoses; Responsiveness measures.

Conclusions: This is possibly the first empirically based multiaxial Neuropsychiatric Consciousness study. In the neuropsychiatric contexts, EPIC Consciousness classifications appear:

Detailed EPIC classification facilitates greater phenomenological neuropsychiatric differentiation.

Background: Episodic symptoms linked with the brain are possibly the most under-diagnosed of all medical conditions: They don’t officially exist. These paroxysmal disorders are often ignored because patients appear well between episodes which often last seconds or minutes. Paroxysmal conditions manifest with varied diagnoses and syndromes. Their evaluations and management necessarily require nonapproved medications. For two decades, we’ve recognized several major episodic conditions. We call these “Paroxysmal Neurobehavioral Disorder” (PND). PND seldom manifests with frank seizures, yet shows subtle behavioral, cognitive, affective phenomena, headaches or temporal lobe symptoms mesial. EEG might show abnormal electrocerebral firing or temporolimbic features. We call one variant “Paroxysmal Photosensitive Disorder.” Objective: Analysis of symptom clusters in episodic conditions aiming at clarifying syndromes or diagnoses. Methods: Methodology: Data evaluated by ordinal change over time applying standard PNI clinical extensive evaluation measures (INSET, SOBIN, Video Ambulatory EEG, Diagnostic Screen-10) anticonvulsant and other medications. Statistics: Nonparametric (e.g. Fisher’s exact). Sample: Appropriate successive clinically consenting neuropsychiatric patients. Results: Emergence of an episodic target symptom cluster (ETSC) responsive to anticonvulsants plus adjuncts compared with other populations with normal AEEG plus no ETSCs. Episodic symptoms analysis show great significance (p<0.001). Conclusions: The PND subgroup classically manifests clinically with severe explosive behavior, marked mood lability and “blankings”± headache, or postevent sleepiness or nausea. PND patients predictably respond to appropriate anticonvulsant plus adjuncts irrespective of whether these patients have abnormal home ambulatory electroencephalograms on three days of monitoring. The data are replicable, reliable, predictable and feasible suggesting PND is a valid entity.

Objective: Predict the results of NESS and reliability, validity and intratest score correlations

Methods: Analysis: Sample: 20+Neuropsychiatric patients until 200+NESSes.

Comparisons: Clinical extensive workup (DS-10, AEEG), Pharmacological responses.

Statistical: Correlative, Nonparametric, ordinal analyses.

Results: The NESS demonstrated:

Variation between different items:

NESS Conclusions:

Background: Delusional misidentification has been estimated to occur in about 15% of patients with Alzheimer’s Disease (AD) and accounts for from 25%−50% of delusions in AD. Capgras, the most common delusional misidentification syndrome, includes the conviction that a close person is an imposter. Delusional misidentification of familiar places and objects also occurs in AD. Antipsychotics are often used with variable responses. Donepezil has been shown to improve other types of delusions in AD and has resulted in improvement of the Capgras delusion in Dementia with Lewy Bodies. To our knowledge, there is no published report on the use of donepezil for delusional misidentification of places and objects in AD. Case History: An 88 year-old Caucasian woman with macular degeneration, hypertension, AD and no past psychiatric history presented for complaints of confusion and poor memory. Her family reported that for about a year she had experienced her bedroom, her clothing, and her shoes as unfamiliar, and denied they belonged to her. On one occasion she also did not recognize her husband. Medication at presentation included memantine 5 mg/day. She was started on donepezil with titration to 10 mg per day. At 2-month follow up, her family reported that she no longer complained of unfamiliarity of her bedroom nor clothing. Conclusions: Feelings of familiarity may be distorted in AD. Although relatively rare and often difficult to treat, delusional misidentification of places and objects in AD may respond to donepezil.

Background: “Visual snow” is a unique and distinct clinical syndrome in which individuals experience persistent black and white dots throughout the visual field that are often described by patients as appearing “static-like” or “grainy.” Additional diagnostic criteria include (i) symptoms from migraine aura and (ii) symptoms are not a result of the pathophysiology of ophthalmological disease or illicit drug use. Case History: Patients with visual snow syndrome often experience entoptic phenomena, impaired night vision, palinopsia, migraines, and tinnitus. A high comorbidity has been found with migraines (approximately 59%) suggesting shared pathophysiological mechanisms; however the clinical presentation differs significantly. A case report of an 18-year-old male presenting with continual visual perception of tiny flickering dots throughout visual field and gradual vision graying with childhood onset, with a normal ophthalmological exam and no history of migraines or illicit substance use is discussed. Patient’s visually-represented description of symptoms and results from a comprehensive neuropsychological evaluation will be provided. Conclusions: Visual snow syndrome is a rare phenomenon that has not been discussed at length in the literature. As a result, it is often misdiagnosed as persistent migraine aura, malingering, or related to a psychogenic disorder or drug use. One recent imaging study investigating the etiology of visual snow syndrome found hypermetabolism in bilateral lingual gyrus and the anterior lobe of the left cerebellum in these patients in comparison to gender and age matched healthy controls. Currently, there are no known treatments.

Background: Psychiatric crisis centers are a recently developed healthcare delivery model designed to assess and triage a large volume of patients presenting with a wide variety of psychiatric symptoms. Effective operation of this system requires rapid assessment and treatment of psychiatric emergencies in part to efficiently utilize frequently insufficient community resources. We present a case in which the diagnosis and treatment of a rare and potentially fatal disorder, anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, was substantially delayed by systems issues with this model. Case Report: A 27 year old female with a history of depression and recent negative neurological workup presented under an involuntary hold to a crisis center with three months of worsening depression and emergence of psychosis with progression into catatonia. Examination was remarkable for catalepsy, waxy flexibility, stereotyped hand movements, alogia, unresponsiveness, and facial grimacing. No autonomic dysregulation or neurological abnormalities were observed and psychiatric hospitalization was pursued. With no available beds and legal limitations regarding consent for psychiatric treatment she remained there over a week and further decompensated before admission until a diagnosis of high-titer, ANA and SSA positive, auto-immune anti-NMDA receptor encephalitis was made. Only partial clinical improvement was achieved with IVIG and steroid treatment and rituximab IV infusions. Conclusions: A nationwide shortage of psychiatric resources has facilitated the creation of crisis centers to triage patients presenting with acute symptoms. Complex and rare illnesses such as anti-NMDA receptor encephalitis present a unique challenge for psychiatrists, who must maintain a high index of suspicion in this clinical setting.

Background: Amygdala-cortical networks have been associated with social behavior. Previous work has defined an ‘aversion’ network, anchored in the dorsal amygdala, associated with pain processing and social avoidance, and an ‘affiliation’ network, anchored in the medial amygdala, associated with prosocial behavior. Resting state functional connectivity MRI (rsFCMRI) in these networks may be altered in schizophrenia. Objective: To compare the strength of functional connectivity within the aversion and affiliation networks in schizophrenia and controls. We hypothesized that functional connectivity strength of the aversion network would correlate positively with positive symptom severity, while connectivity strength of the affiliation network would correlate negatively with negative symptom severity. Method: Subjects included 30 patients with schizophrenia, assessed with the Positive and Negative Syndrome Scale, and 30 age- and sex-matched controls. Resting-state functional MRI data were processed using established processing streams previously published in Bickart et al (2012). For each subject, we calculated FC strength within the dorsal and medial amygdala networks. FC between controls and patients was compared with unpaired t tests, and symptom subscale correlations within patients were evaluated with spearman’s correlations. Results: FC in both the aversion and affiliation networks was diminished in schizophrenia compared with controls, reaching significance for the dorsal amygdala (aversion) network (t=2.0, p=0.047). A correlation between FC of the affiliation network and PANSS negative subscale trended toward significance (rho=−0.290, p=0.06, one-tailed). Conclusion: Functional connectivity strength within amygdala-cortical networks was decreased in schizophrenia.

Background: The C9orf72 repeat expansion is a recently discovered autosomal genetic alteration that is associated with some familial cases of behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS). Objective: To characterize symptom profiles and structural brain changes of individuals with the C9orf72 repeat expansion and bvFTD or FTD-ALS. Methods: Subjects included 10 individuals with bvFTD or FTD-ALS and the C9orf72 repeat expansion, eight of whom had structural MRIs for analysis. Freesurfer 5.3 was used to process images and extract structural measures using standard workflows. Selected subcortical and cortical regions were compared with those in a set of normal older adults using unpaired two sample t tests and corrections for multiple comparisons. Single subject cortical thickness maps were also constructed to evaluate regions of atrophy compared with normal older adults, using a generalized linear model. Clinical histories were reviewed regarding criteria for bvFTD and psychotic symptoms. Results: Subcortical volumes including the bilateral thalami, hippocampi, and amygdalae, but not cerebellar cortices, were significantly diminished in subjects (p-adjusted<0.05). Cortical thickness analyses revealed significant bilateral atrophy most prominent in orbitofrontal, superior frontal, and middle temporal regions. Nine patients satisfied clinical criteria for possible bvFTD, four had delusions, and three had mild auditory hallucinations. Conclusion: In this sample, individuals with the C9orf72 repeat expansion and bvFTD or FTD-ALS demonstrated significant atrophy in subcortical regions and frontotemporal cortices, and had a moderate prevalence of psychotic symptoms, which is atypical for bvFTD but has been described in patients with this genetic alteration.

Background: Current nosology of primary progressive aphasia (PPA) recognizes 3 forms: semantic dementia, progressive nonfluent aphasia (PNFA), and logopenic aphasia (LPA). PNFA is characterized by effortful speech production secondary to agrammatism and/or apraxia of speech and most commonly associated with tau pathology. LPA patients have word retrieval impairment with phonological deficits and underlying Alzheimer’s pathology. Few studies have explored a possible relationship between recurrence of a childhood language-based disability and development of an atypical neurodegenerative process. Case History: A 61 year-old right-handed man with developmental history of stuttering and expressive language difficulty presented for recrudescence of stuttering and new onset of word finding difficulties. He was a college graduate and successfully employed in a high level sales position. Neuropsychological testing 7 months prior, had revealed cognitive dysfunction in numerous domains. On evaluation, his speech was halting, stuttering, circumlocutory, and he had difficulty repeating complex utterances, but no dysarthria. Elemental neurological examination was unremarkable. MoCA score was 16/30. Brain MRI showed mild regional left perisylvian atrophy; integrated FDG PET MRI revealed asymmetric focal hypometabolism of the left superior and mid temporal gyrus. CSF was noninflammatory, pending results for dementia biomarkers. Repeat neuropsychological evaluation after 9 months demonstrated further decline in visual learning and recall, verbal expression, and dramatic decline in nonverbal reasoning. Conclusions: This case indicates that future studies should explore whether recurrence of a childhood language disability is an initial presentation of a diffuse degenerative process or a predisposition to developing an atypical neurodegenerative condition later in life.

Background: Functional Neurological Symptoms (FNS) are prevalent neuropsychiatric presentations, yet efforts to develop specialized clinics for this population remain limited in the U.S. Objective: This retrospective study investigated predictors of adherence to outpatient referral, symptom severity and FNS subtype in a Functional Neurological Disorders clinic. Methods: Medical records from August 2014-July 2015 for 62 consecutive patients (16 men: 46 women) with suspected FNS were reviewed. A series of multiple regression analyses were conducted using SPSSv23. For the 49 patients with FNS attending the initial visit, analyses investigated demographic and clinical variables associated with verbal-reported symptom severity and total number of functional examination findings. Exploratory analyses probed variables associated with motor FNS subtypes. Results: Emergency Department (ED) referrals were associated with outpatient nonadherence (p=0.022). In 49 individuals who showed, self-reported symptom severity was linked to a history of FNS-related ED visits (p=0.029) and a diagnosis of another medically unexplained syndrome (p=0.007). Total number of functional examination findings was also predicted by a history of FNS-related ED visits (p=0.005). Individuals with Psychogenic Nonepileptic Seizures more frequently endorsed cognitive complaints (p=0.002) and a history of psychiatric hospitalization (p=0.015); patients with functional weakness reported a greater number of overall symptoms (p=0.005) and fewer cognitive complaints (p=0.06). Conclusions: Individuals presenting to the ED with FNS may have lower adherence rates to specialized outpatient referral. Greater symptom severity was observed in those with a history of FNS-related ED visits and another medically unexplained syndrome. Integrated clinical research programs and prospective data collection across the FNS spectrum may further elucidate common and subtype-specific disease effects.

Background: Traditionally, neurodegenerative disease is treated by a combination of family, primary care physicians, nursing home staff and consulting neurologists. This model leaves gaps in the care of these patients, who frequently have behavioral problems, incapacity for decision making, and multifactorial physical complaints. Palliative care is most commonly practiced by internists, who may be less comfortable with palliation of symptoms due to neurologic illness than nonneurologic illness. An interdisciplinary palliative care clinic focused on neurodegenerative disease was developed at University of Colorado Hospital (UCH). Objective: To describe the UCH palliative care clinic for neurodegenerative disease with the goal of program evaluation and improvement. Methods: Palliative care clinic encounters from 10/1/2014–10/1/2015 were reviewed for patient demographics, diagnosis, reason for referral, completion of advanced directives and resource utilization. For deceased patients, location of death was recorded. Results: 200 clinical encounters were reviewed. The most common diagnosis was Parkinson disease (37%), followed by Parkinson disease dementia, multiple sclerosis, and progressive supranuclear palsy. The average age was 65. The most common reason for referral was “psychosocial support,” followed by “discussion of goals of care,” “complex symptom management,” and “care giver support.” All patients saw the physician on each visit, while only 63%, 77% and 91% of encounters involved the specialty nurse, chaplain and social worker respectively. Conclusion: The palliative care clinic is feasible, and offers a promising model for addressing the complex clinical needs of neurodegenerative disease patients at UCH.

Background: Yearly in the United States, an estimated 2.5 million civilians suffer traumatic brain injury (TBI). Diagnosis of TBI remains a challenge and there is an unmet clinical need for accessible biomarkers that can accurately and reliably detect TBI and predict TBI-associated consequences. Objective: The Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART) study was designed to examine the utility of blood-based biomarkers for acute diagnosis of TBI and prognostication of TBI-related neurocognitive and neuropsychiatric sequelae. Methods: HeadSMART is a six-month prospective cohort study with one exposure group (patients evaluated for TBI in the emergency department) and two control groups: (1) traumatically injured non-TBI and (2) healthy. Collection of blood for biomarker levels occurs at multiple time points (acutely, subacutely, and long-term) after injury. An extensive neurocognitive and neuropsychiatric battery is completed at 1, 3, and 6 months. As the study is ongoing, here we present characteristics of thus far screened and enrolled participants. Results: Of 1778 patients presenting to the hospital with head trauma, 300 were enrolled as TBI participants in HeadSMART. Seventy percent of participants met American Congress of Rehabilitation Medicine (ACRM) criteria for TBI and of ACRM positive individuals, 80.1% had mild TBI. Among all participants, the majority had Glasgow Coma Scale scores of 13–15 (98.0%), normal head CTs (81.3%), and no prior history of concussion (71.7%). Conclusion: HeadSMART is a unique, systematically phenotyped cohort that will make significant contributions to current understanding of the use of blood-based biomarkers in TBI evaluation and management.

Background: Little is known about traumatic brain injury (TBI) associated neuropsychiatric disturbances (NPDs) in the elderly, though mortality and morbidity are significantly worse in the elderly compared with the younger population¹. Studies suggest that poor outcomes among the elderly are mediated by medical comorbidity². However, NPD can also contribute to disability and poor quality of life. Objective: To quantify risk of NPD among Medicare beneficiaries following TBI. Methods: We conducted a retrospective analysis of Medicare administrative data obtained from the Centers for Medicare & Medicaid Services Chronic Condition Data Warehouse. Medicare beneficiaries hospitalized with TBI from 2006–2010, discharged alive, aged≥65, with no history of depression prior to 2006 and continuous Medicare coverage were included in the analysis. We calculated unadjusted rates of depression, anxiety and posttraumatic stress disorder (PTSD) pre- and post-TBI and used generalized estimating equations to generate adjusted risk ratios. Results: Sample size was 66,238. Rates of depression, anxiety and PTSD per 1,000 person-years pre-TBI were 76.9, 54.0, and 0.6, respectively. Rates of new onset NPDs post-TBI per 1,000 person-years were 112.5 (depression), 60.8 (anxiety) and 1.1 (PTSD). Adjusting for demographics and comorbidity, TBI increased risk of depression (relative risk (RR) 1.11; 95% confidence interval (CI) 1.08, 1.15) and PTSD (RR 1.50; 95% CI 1.13, 1.99) but not anxiety (RR 0.90; 95% CI 0.87, 0.93). Conclusion: TBI significantly increases risk of new onset depression and PTSD in the elderly. Increased screening and treatment of depression and PTSD following TBI may help to reduce morbidity and disability in this fragile population.

1. Krishnamoorthy V, Distelhorst JT, Vavilala MS, et al: Traumatic Brain Injury in the Elderly: Burden, Risk Factors, and Prevention. J Trauma Nurs 2015; 22:204–208, quiz E3–E4

2. Papa L, Mendes ME, Braga CF: Mild Traumatic Brain Injury among the Geriatric Population. Curr Transl Geriatr Exp Gerontol Rep 2012; 1:135–142

Background: People with Intellectual and/or Developmental Disabilities (I/DD) are known to be at risk for earlier age of death from multiple medical conditions and are posited to receive less than standard care for their conditions. This study is intended to help advance our understanding of health outcomes in the I/DD population. Case/Methods: We have performed mortality reviews for adult individuals with I/DD (age range 21–92 years). We conducted reviews of available summary records and treatment in the last year of life for 45 individuals with multiple medical comorbidities with I/DD. Of those, fewer than 15% had autopsy confirmation of cause of death and comorbidity. We also reviewed all available notes during the last year of life. It is clear that information is often not available to all people involved in supporting the person with I/DD in a consistent fashion. Patterns were identified of comorbidities that affect each other. Additional findings included examples of lack of shared knowledge between specialists and direct care providers who were not guardians. This leads to a clear break down in communication within the team providing support and puts the identified individual at risk for complications. Extraordinary quality of life and coping with chronic illness was also identified. Conclusions: Patterns of association between known and observed comorbid conditions are illustrative of the challenges facing an aging population with I/DD. The need for supporting autopsy examination as a means for ongoing education is evident.

Background: Few studies have examined the clinical correlates of aggressive behavior after TBI. Objective: Our study aims to 1) identify the occurrence of aggression at 6 months and 12 months after TBI and 2) to establish the demographic and clinical correlates of aggression at 6 months and 12 months after TBI. Methods: Subjects with first-time TBI were recruited from the acute trauma units within three months of trauma and followed at 6 and 12 months after TBI. The Overt Aggression Scale (OAS) was used to examine 4 domains of aggression. Results: Rates of aggression at 6 and 12 months were found to be 41.1% and 38.0% respectively. Verbal aggression was the most prevalent subtype of reported aggression in the post-TBI period; 41.1% and 38.0% at 6 and 12 months respectively. Body injury was associated with aggression at 6 months (β=1.43 p=0.014). Those with aggression had less total years of education (12.2) than those with no aggression (13.6); p=0.04. Male gender was associated with aggression at 12 months (β=-1.05; p=0.04). Poor social functioning at 3 months after TBI was associated with aggression at 12 months after TBI (β=4.77; p=0.02). There were no statistically significant differences in any other demographic variables. Conclusions: Post-TBI social functioning, education level, gender and the presence of body injury may serve as predictors for post-TBI aggression. Aggression at 6 months and 12 months is not associated with psychiatric comorbidity, and its presence at 6 months predicts aggression at 12 months. Literature begs for further investigation.

Background: Psychiatric disorders are highly prevalent in Multiple Sclerosis (MS) but under-recognized and under-treated. The Sonya Slifka Longitudinal MS Study is a study of 2,156 people with MS that broadly reflects the MS population in the U.S. It provides valuable data to address gaps in our understanding of mental disorders in MS. Objectives: The goals of this study were to estimate the prevalence of emotional distress in the Slifka Study sample and examine its relationship to demographic, disease, and health care characteristics. Methods: The sample included 2,156 people with MS in the US. We conducted computer assisted telephone interviews to collect data on: Demographics; disease characteristics; health care characteristics; mental health treatment. Results: Almost half of the respondents experienced psychological distress, moderate or severe. Because of emotional problems, 46% of respondents felt they had accomplished less and 31% felt they had done work less carefully than usual. Respondents with psychological distress were more likely to be younger, divorced or never married, unemployed, and to have less education and lower income. Psychological distress was associated with more MS relapses, moderate disability, and poorer perceived health. Respondents with psychological distress were more likely to lack health insurance and to have problems accessing medical and mental health care. Conclusion: Psychological distress is highly prevalent in MS and has a negative impact on individuals’ functioning and quality of life. Further efforts are needed to improve access to mental health care for this population.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common comorbidity in pediatric epilepsy, with a prevalence approximating 40%. The predominantly inattentive subtype of ADHD may be particularly common. Less is understood about the impact of specific epilepsy subtypes upon ADHD comorbidity. Objective: Assess whether ADHD symptom presence varies depending upon epilepsy subtype. Methods: A retrospective review was conducted from a tertiary care Neuropsychiatry and Epilepsy Specialty Outpatient Program. The records were obtained over a one year period from a clinical sample of prospectively collected data. Case records from 36 children and adolescents with full data, all of whom had confirmed epilepsy were included. The sample was restricted to those with average range IQ. All patients underwent clinical evaluation, and caregivers completed standardized questionnaire measures assessing general psychiatric symptoms including executive function and ADHD symptoms (Swanson, Nolan and Pelham Scale: SNAP). Results: 21 children had generalized seizures (age range 3–16, average 9.28, 17 male). 15 children had focal seizures (age range 5–17, average 11.15, 14 male). On the SNAP scale, overall ADHD symptoms were more common in the generalized epilepsy group than in the focal epilepsy group (Chi-square 5.143; Fisher exact test: p=0.0409). On a global executive function measure (BRIEF), the generalized epilepsy group had worse function than the focal group, but only trended toward significance (Chi square 3.540; Fisher exact test: p=0.0599). Conclusion: ADHD may be more common in children with generalized epilepsy than with focal epilepsy. Further study with a larger sample size is necessary to confirm results.

Background: Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disease that occurs in (predominantly male) carriers of the FMR1 premutation. FXTAS manifests with intention tremor, ataxia, parkinsonism, peripheral neuropathy, psychiatric symptoms (especially depression and anxiety) and, later in the course of the illness, cognitive changes, including dementia. To date, factors that predispose patients with FXTAS to dementia have not been clearly elucidated. Objective: To identify risk factors for FXTAS dementia. Methods: This was a retrospective chart review of 53 cognitively impaired patients with FXTAS (ten women, 43 men; mean age=68.2 years, SD=7.6) evaluated between 2004 and 2014 at a large research center. Presence of risk factors for dementia was examined, including CGG repeat size, alcohol and opioid use, diabetes mellitus, hyperlipidemia, hypertension, hypothyroidism, sleep apnea, surgeries, lifetime history of depression, and family history of dementia. Descriptive statistics were summarized as the mean±SD or frequency (%). In a subset analysis, fourteen individuals with FXTAS and dementia were compared with fourteen cognitively intact individuals matched on age, gender, and FXTAS stage, using chi-square (Fisher’s exact) tests. Results: There were no significant differences for any of the risk factors assessed, except for CGG repeat size, which was significantly higher (mean=97.1, SD=20.7) in the dementia group, compared with the cognitively intact group (mean=82.9, SD=12), p=0.0342. Conclusion: Higher CGG repeat size may be a risk factor for FXTAS dementia. Further studies are necessary to replicate this finding.

Background: Neurologic diseases often share overlapping symptoms with psychiatric conditions. For example, temporal lobe seizures may manifest with psychosis, mood changes, obsessional thinking, compulsive behavior, personality changes and/or other nonspecific mental health symptoms. Psychosis is the defining characteristic of schizophrenia and may be an associated finding of temporal lobe epilepsy. Schizophrenia is fundamentally a diagnosis of exclusion. As such, the presence of psychosis requires consideration of other potential concurrent and/or independent etiologies including temporal lobe seizure activity. Case History: This is a case of long standing schizophrenia in a patient adherent with clozapine (200/200/450) who presented with worsening perceptual disturbances and confusion that was presumed to be an aggravation of their schizophrenia. The patient’s clozapine was continued along with addition of haloperidol and lorazepam. The patient’s condition worsened despite the above interventions which prompted consideration for antipsychotic related seizure activity. As such, a brain MRI (will be included) was obtained which demonstrated a temporal lobe mass. Follow up 30 min. EEG was not consistent with seizure activity; however, there was concern that the EEG simply did not detect an active seizure given the MRI noted potential seizure focus. As a precaution, divalproex SA 1000 mg daily was added to the patient’s clozapine with subsequent symptomatic improvement while haloperidol and lorazepam were discontinued. Conclusion: Temporal lobe epilepsy share clinical characteristics with psychiatric conditions such as schizophrenia. If seizure activity-related psychosis is misattributed to schizophrenic psychosis, subsequent efforts to control psychosis with antipsychotic therapy can complicate the epilepsy course by lowering the threshold for seizures. When seizures and psychosis present together in the setting of antipsychotic use, it can be difficult to determine whether both processes are independently occurring, the seizure activity is driving the psychosis or the antipsychotic management is generating seizures. Use of clozapine at doses≥600 mg/day is associated with a greater risk of seizures (4.4%). When clinically warranted, prolonged EEG or MRI testing may be indicated to differentiate between these two potentially overlapping conditions.

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Introduction: The temperament and character inventory (TCI) quantifies seven personality traits with established neurobiologic bases. We have previously identified TCI Persistence as a candidate predictor of antidepressant response to repetitive Transcranial Magnetic Stimulation (rTMS). This was attributed to preliminary optical neuroimaging data showing that unilateral cortical excitability is inversely related to Persistence (P) and directly related to Novelty Seeking (NS). Objectives: To demonstrate the relationship of cortical excitability with P and NS by using rTMS resting motor thresholds (RMT), which are inversely related to cortical excitability. Methods: Twenty depressed adults completed a TCI prior to a course of left-sided rTMS with baseline RMT measurement. Pearson coefficients were calculated for baseline RMT in comparison with P, NS, and the ratio of P/NS. For ten subjects who underwent augmentative right-sided rTMS as clinically indicated, left-right asymmetry between RMTs was also compared with P, NS, and P/NS. Results: Baseline left-sided RMT was directly related to P (R=0.45, p=0.04) and P/NS (R=0.66, p=0.001), while left-right RMT asymmetry was inversely related to NS (R=−0.69, p=0.03). The other five personality traits showed no correlation with left-sided RMT (p>0.52) or with RMT asymmetry (p>0.22). Conclusions: This study used a novel approach to support the association of Persistence and Novelty Seeking with cortical reactivity. Persistence was inversely related to left-sided cortical excitability and Novelty Seeking was directly related to asymmetry in cortical excitability. This lends further credence to the notion that personality-related variability in rTMS response may be associated with cortical excitability changes.

Background: Epilepsy is associated with neurocognitive and neuropsychiatric changes including increased risk for suicide. Case History: A 52-year-old, right-handed male with epilepsy and visual deficits secondary to an accidental, occipital gunshot wound (GSW) from work and a preceding history of head injuries was referred for pre- and postsurgical neuropsychological testing to assess neurocognitive and neuropsychiatric functioning. He was tested prior to epilepsy surgery in 2013 and then postsurgery in 2015. Initial testing showed largely intact language and verbal memory and impairments in attention, working memory, and verbal fluency. He was also diagnosed with major depressive disorder, severe and posttraumatic stress disorder (PTSD). His fears of having seizures in public leading to social isolation along with his suicidal ideation, substance abuse, gun collection, and marriage separation placed him at high suicidal risk. He was then referred for temporary partial care; however, treatment did not effectively target his neuropsychiatric symptoms. Despite postsurgical improvements in verbal fluency and set-shifting and resolution of substance abuse and seizure-related phobia, he continued to display symptoms of severe depression, PTSD, passive suicidal ideation, and emotional lability. Conclusions: The occipital lobe GSW, subsequent epilepsy, and visual deficits led to functional status changes. Despite improvements in executive functions, resolution of substance abuse and increased social support, clinically elevated neuropsychiatric symptoms were observed at follow-up testing. Other potential comorbid factors for mood symptoms included continued seizures and prior history of head injuries. The persistence of untreated symptoms over time illustrates the need for targeted care in complex neuropsychiatric epilepsy cases.

Background: Whipple’s disease (WD) is a rare disease that affects multiple organ systems with highly variable clinical presentations. WD is a systemic infection of Tropheryma whipplei which may present systemically or with neuropsychiatric signs and symptoms. Untreated WD can be fatal in a significant number of patients. While diagnostic testing is often inconclusive and MRI findings vary, oculomaticatory myorhythmia has been identified as pathognomonic to WD. Case History: A 65 year old woman with history of obstructive sleep apnea, asthma, hypertension, and unspecified bipolar disorder presented with suicide attempt via overdose, worsening depression, confusion, lethargy and increasing falls over the past several months. Examination was significant for impairment in multiple cognitive domains, stiffness and right palmomental reflex and fluctuating mental status. The patient later demonstrated catatonic symptoms that were responsive to lorazepam without a clear etiology. As work-up continued, she was noted to have oculomasticatory myorhythmia with supranuclear gaze palsy. With concern for possible WD, gastroenterology performed endoscopy with biopsy. By the next day, she rapidly decompensated and was treated for malignant catatonia. While awaiting PAS staining from duodenal biopsy, presumptive treatment with ceftriaxone was initiated with rapid improvement in neuropsychiatric symptoms that was sustained six months after treatment began while continuing doxycycline and hydroxychloroquine. Conclusions: This case demonstrates subtle features that may be associated with a WD diagnosis and the challenges of conclusive diagnosis. Additionally, the presence of concurrent catatonia symptoms may provide further insight into the etiology of CNS Whipple disease, which has historically been poorly characterized.

Background: It is believed that the best hope of treating Alzheimer’s disease (AD) will be to intervene before clinically significant cognitive decline develops. Neuroimaging can detect disease preclinically but the clinical significance in individual patients is uncertain. Objective: To examine the feasibility of using volumetric MRI and FDG PET data for predicting the subsequent development of amnestic Mild Cognitive Impairment (aMCI) in cognitively unimpaired (CU) individuals. Methods: From an Arizona longitudinal study of aging, we examined the FDG PET and MRI data from 18 CU subjects approximately 2 years (1.84±0.77) before development of aMCI and 35 age and sex matched participants who remained CU for ≥4 years. FDG-PET and MRI regions of interest were used separately and in combination to examine the sensitivity and specificity in distinguishing the two groups using binary logistic regression technique, receiver operating curve and leave-one-out approach. Results: Compared with nonconverters, those who developed aMCI in approximately 2 years had significant decreases in glucose metabolism, gray matter volume, and cortical thickness in regions known to be affected by AD. The imminent aMCI group also showed relative increased glucose metabolism in the left and right pre and post central gyrus. The best single predictor of aMCI was left hippocampal volume, with 74% sensitivity and 72% specificity. Combining MRI and FDG PET data increased the sensitivity and specificity of the predictive model to 77% and 78%. Conclusion: Imaging based biomarkers can potentially be used for CU individuals to predict imminent aMCI, particularly when different neuroimaging modalities are combined.

Background: Agraphesthesia has been attributed to impairment of the ability to detect more rudimentary directionality of lines written on the skin (directional cutaneous kinesthesia). We examined two patients who had a dissociation between preserved perception of line directionality and the loss of graphesthesia for letters and numbers. Case History: Two patients with right parietal tumors were tested for the ability to determine the directionality of lines drawn on the palms and forehead and then evaluated for recognition of letters and numbers in these regions. Our patients could identify the directions of lines, letters and numbers drawn on paper. The ability to detect the direction and shape of lines drawn on the skin of the palms and on the forehead was preserved but they had agraphesthesia for numbers and letters in these same locations. Conclusion: The finding of isolated agraphesthesia for letters and numbers may be assigned to damage in the right parietal lobe. It represents a deficit of somatosensory processing that is of a higher order than detection of line directionality. The term “tactile asymbolia” may capture the dissociation. These clinical findings suggest that tactile cortex in humans, like visual cortex, may be hierarchically organized, as has been demonstrated in primates.

Background: Chronic Traumatic Encephalopathy is a neurodegenerative condition that occurs as a consequence of repeated mild head injury. This condition is distinct from postconcussive syndrome. Symptoms do not emerge until years after the trauma. CTE is pathologically distinct from other neurodegenerative conditions. It was initially described in boxers and more recently has been found in professional football players, military veterans, hockey players, and other athletes. As of yet there are no standardized criteria for diagnosing this disease clinically.¹ Case History: M.O. is a 49 year old woman with a history of a physically abusive marriage from age 19 to age 34 who was well until roughly age 47 when she stopped working due to her concerns that she could no longer do her technical job. She initially presented to our care in 2012 with persistent SI. She had impairment in attention, memory loss, and profound depression. She had experienced a severe decline and became emotionally reactive and impulsive. She was treated with a combination of stimulants and anticonvulsants with dramatic improvement in attention, memory and mood. Conclusions: To our knowledge this is only the second case report in the literature of probable CTE from domestic violence² and one of only a handful of CTE cases described in women. We believe that this population of patients is at substantial risk for this condition. It is our hope to call attention to consideration of this diagnosis and to encourage further study especially in the development of clinical diagnostic guidelines.

1. Baugh CM, Stamm JM, Riley DO, et al: Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav 2012; 6:244–254

2. Roberts GW, Whitwell HL, Acland PR, Bruton CJ. Dementia in a punch-drunk wife. Lancet 1990; 355:919–920

Background: Genomic disorders are of increasing relevance to neuropsychiatric practice. The most common genomic disorder is the 22q11.21 deletion syndrome, also known as DiGeorge syndrome (DGS) or velocardiofacial syndrome (VCFS). Individuals with 22q11.21 deletion syndrome are at increased risk of intellectual disability, autism spectrum disorders, psychosis, and epilepsy. Chromosome 22 is rich in low-copy repeats (LCRs), and is therefore prone to deletions and duplications by nonallelic homologous recombination. The clinical significance of deletions and duplications outside the DGS/VCFS region on chromosome 22 are less well known. Case History: The area of copy number variation in DGS/VCFS is most commonly a 3 Mb region from LCR22-A to LCR22-D, and less commonly a 1.5 Mb region from LCR22-A to LCR22-B. We describe a case series of four patients with a 200 kb duplication between LCR22-G and LCR22-H diagnosed on microarray, which is thought to be a benign polymorphism. These patients all have intellectual disability. They have variable phenotypes with some also having autism spectrum, depressive, psychotic, anxiety, and impulse control disorders, as well as epilepsy. Conclusions: This case series suggests that 22q11.22 duplication between LCR22-G and LCR22-H may not be a benign polymorphism, but a novel risk locus for multiple neuropsychiatric disorders with highest penetrance for intellectual disability. Consistent with previously described 22q11 deletion and duplication syndromes, the patients in this case series have variable phenotypes likely with incomplete penetrance. The genotype-phenotype relationship remains unclear, thus highlighting the need for continued reporting of neuropsychiatric cases with genomic abnormalities.

Background: Mood disorders and neurocognitive impairment represent serious disabilities among patients with HIV/AIDS. The interaction of these factors and their contribution to neuropsychiatric disability remains uncertain. Objective: To investigate the relationships between depression, neurocognitive performance and HIV-associated neurocognitive disorder (HAND). Methods: 298 HIV-1 seropositive patients were enrolled randomly in a cohort study with neurocognitive status as the primary outcome measure. Severity of depressive symptoms was assessed using the PHQ-9 questionnaire and staged by standard PHQ-9 categorization. All patients were assessed by z-scaled performance in a multidomain neuropsychological test battery, as well as by clinical, neuroimaging and demographic features verifying the diagnosis of HAND. Univariate, contingency and regression analyses were used to test the interactions between depression severity, neurocognitive performance and HAND diagnosis. Results: Depression categories included: minimal (N=159; PHQ-9, 0–4), mild (N=65; PHQ-9, 5–9), moderate (N=40; PHQ-9, 10–14) moderately severe (N=22; PHQ-9, 15–19) or severe (N=12; PHQ-9, 20–27). 46.6% of patients exhibited at least mild depressive symptoms. Cumulative neurocognitive performance (Z_total) was worse among patients with moderate to severe depression (ANOVA, p<0.0005) than in patients with mild depression. Neurocognitive status (Z_total) correlated negatively with PHQ-9 (p<0.005) in all patients particularly in attention and memory domains. PHQ-9 score was unrelated to current/nadir CD4+T-cell count or viral load. The proportion of patients with HAND (N=58) was consistently represented in all PHQ-9 subgroups (p>0.05). Conclusions: Depression is common in HIV/AIDS and constitutes a substantial comorbidity associated with worsened neurocognitive performance. Independent of HAND diagnosis, these findings highlight the importance of screening for mood disturbances among patients with HIV/AIDS.

Background: Post-stroke depression (PSD) is a disabling condition occurring in about one-third of stroke patients. Pharmacological treatments present limited efficacy and important side effects. Recently, transcranial direct current stimulation (tDCS) has shown efficacy in depression treatment. Objective: Our aim was to assess the efficacy and safety of tDCS for PSD. Method: Forty-eight antidepressant-free patients who developed PSD were randomized in two groups (active and sham tDCS). Twelve 30-minute sessions of 2-mA anodal left/cathodal right dorsolateral prefrontal tDCS were applied over 6 weeks (10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week). The primary outcome measure was the change in Hamilton Depression Rating Scale 17 items score at 6 weeks. Results: Active tDCS was significantly superior to sham at endpoint (mean difference, 4.7 points; 95% CI, 2.1 to 7.3; p<0.001), but not at weeks 2 and 4. Response and remission rates were also statistically higher in active (37.5% and 20.8%, respectively) versus sham (4.1% and 0) groups, with a number-needed-to-treat of 3 and 5, respectively. No serious adverse effects were reported and the frequency of common adverse effects was similar in both groups. Patients and raters were effectively blinded. Conclusions: This is the first controlled study demonstrating that tDCS was safe and effective for PSD. Therefore, tDCS might be an option for the treatment of these patients.

Background: The anterior insula (AI) is implicated in subjective feelings of physiological states and representation of aversive states and risk and recently in the transition toward compulsive behaviors. These constructs are highly relevant in disorders of addiction. Studies from stroke patients and transcranial magnetic stimulation show that anterior insula lesion are associated with a decreasing in smoking urges. Objective: To assess resting state functional connectivity of the AI and striatum across healthy controls and alcohol dependence and examine the relationship with clinical and cognitive variables. Methods: Healthy controls, binge drinkers and alcohol dependent subjects were scanned using multiecho resting state sequence and analyzed using independent components analysis (MEICA). Connectivity between AI seed and striatum were correlated with alcohol severity (AUDIT), habit formation (two-step task), obsessive compulsive inventory (OCI) and impulsivity (delay discounting). Results: Baseline connectivity for both increases and decreases in cortical and subcortical connectivity of the anterior insula were mapped for 160 healthy controls. AUDIT scores positively correlated with AI-striatal connectivity in healthy controls and binge drinkers (N=160). AI-striatal connectivity was decreased as a function of abstinence in alcohol dependent subjects (N=39). In healthy controls, greater habit formation as measured using the two-step task (N=94), OCI severity (N=63), and delay discounting (N=81) were positively correlated with greater AI-striatal connectivity. Conclusion: Our results emphasize connectivity of the AI and striatum across alcohol misuse and compulsivity suggesting a crucial node for therapeutic neuromodulation.

Background: Functional neurological disorders (FND) are neurological symptoms unrelated to a medical cause. Previous small studies suggest impaired subjective awareness of voluntary intention and decreased mesial cortical activity during intention. Intention can be assessed using Libet’s clock in which subjects report the time of the urge to move or the time of the movement. Objective: To assess neural correlates of voluntary intention in FND versus healthy controls using Libet’s clock with task-based and resting state fMRI. Methods: FND (N=26) and healthy controls (N=23) were scanned with Libet’s clock task paying attention to either the intention to move or the actual movement. Task-based and resting state functional connectivity was also assessed. Results: FND subjects had delayed subjective intention to move (W) as compared with movement (M) relative to healthy controls. FND subjects had decreased activity to W-M in right inferior parietal cortex (IPC) and left premotor cortex (PMC), regions also correlating with W-M. During W-M, FND subjects had lower connectivity of RIPC with putamen and LPMC with limbic regions (amygdala, anterior insula) and hippocampus. At rest, FND subjects had lower connectivity between LIPC and other regions implicated in intention including dorsolateral prefrontal cortex and premotor cortex and RPMC with bilateral putamen. Conclusion: Our results emphasize impaired processing of voluntary intention in FND associated with lower inferior parietal and premotor activity and emphasize both task related and resting state impairments in functional connectivity of a network implicated in intention and limbic regions.

Background: We describe a patient that presented with a schizophrenia-like psychosis who was found to have a choroid plexus papilloma. This case adds to a limited number of previous reports demonstrating a possible link between intracranial tumors, specifically choroid plexus papilloma and psychosis in the context of a diagnosis of schizophrenia. Case History: 28 year-old male with a diagnosis of schizophrenia and multiple involuntary psychiatric hospitalizations was admitted for aggressive and bizarre behavior. He demonstrated aggressive behavior and catatonic features, endorsed delusions of control. Testing revealed deficits in verbal abstract reasoning with very concrete thinking. CT demonstrated a partially calcified mass in the frontal horn of the right lateral ventricle and on brain MR was consistent with a choroid plexus papilloma with mild enlargement of the right lateral ventricle. Conclusions: Recent research has demonstrated an overlap between structural brain abnormalities implicated in schizophrenia and the neural substrates involved in cognitive and emotional processing, such as the thalamus. Considering the proximity of this intraventricular mass to the thalamus and involvement of frontal – striatal circuits implicated in schizophrenia, this case adds to the literature on intracranial masses presenting as schizophrenia, and serves to highlight the importance of neuroimaging and medical work-up in the evaluation of psychosis.

Pergola G, Selvaggi P, Trizio S, et al: The role of the thalamus in schizophrenia from a neuroimaging perspective. Neurosci Biobehav Rev 2015; 54:57–75

Johnstone EC, Crow TJ, Frith CD, et al: Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 1976; 2:924–926

Wright IC, Rabe-Hesketh S, Woodruff PW, et al: Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000; 157:16–25

Olabi B, Ellison-Wright I, McIntosh AM, et al: Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol Psychiatry 2011; 70:88–96

Harrison PJ, Freemantle N, Geddes JR: Meta-analysis of brain weight in schizophrenia. Schizophr Res 2003; 64:25–34

Crow T, Chance S, Priddle T, et al: Laterality and sex interactions cross the schizophrenia/bipolarity continuum: an interpretation of structural MRI meta-analysis. Psychiatry Res 2013; 210:1232–1244

Bakhshi K, Chance SA: The neuropathology of schizophrenia: A selective review of past studies and emerging themes in brain structure and cytoarchitecture. Neuroscience 2015; 303:82–102, [Epub ahead of print]. Available at doi: 10.1016/j.neuroscience.2015.06.028

Ouma JR: Psychotic manifestations in brain tumour patients: 2 case reports from South Africa. Afr Health Sci 2004; 4:189–193

Andreasen NC, Paradiso S, O’Leary DS: “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull 1998; 24:203–218

Sherman SM, Guillery RW: Exploring the Thalamus and its Role in Cortical Function, 2nd ed. Cambridge, MA, MIT Press, 2006

Van der Werf YD, Jolles J, Witter MP, et al: Contributions of thalamic nuclei to declarative memory functioning. Cortex 2003; 39:1047–1062

Carson BS, Weingart JD, Guarnieri M, et al: Third ventricular choroid plexus papilloma with psychosis. Case report. J Neurosurg 1997; 87:103–105

Arasappa R, Danivas V, Venkatasubramanian G: Choroid plexus papilloma presenting as schizophrenia: a case report. J Neuropsychiatry Clin Neurosci 2013; 25:E26–E27

Background: Repeated head trauma has been associated with the development of Parkinson’s Disease (PD). The pathoetiology may include disruption of the blood-brain barrier, impaired axonal transport and the accumulation of α-synuclein.^1,2 Posttraumatic PD is known to be especially resistant to pharmacologic intervention, and deep brain stimulation (DBS) is a viable therapeutic option. Major depressive disorder (MDD) is often comorbid with PD; moreover, MDD and other mood disorders have been linked to DBS.^3–5 For patients that develop depressive syndromes after placement of DBS electrodes, electroconvulsive therapy (ECT) has been shown to be effective.^6,7 Case History: A patient sustained a serious motor vehicle accident with loss of consciousness and subsequently developed severe parkinsonian symptoms. Her PD was successfully treated with DBS; however, after a DBS battery change, she rapidly developed malignant depression with suicidal ideation. After numerous trials of medications failed, she underwent ECT with a dramatic positive response. However, this patient’s depressive symptoms progressively reappear with severe anxiety, obsessive thinking, a pervasive sense of doom, and suicidal thoughts. With these symptoms she does not experience signs of a seizure disorder, and her EEG has been unremarkable. Repeating the course of ECT upon relapse of depression has consistently proven effective. Conclusion: i) posttraumatic PD may appear after a single traumatic head injury event, ii) DBS can indeed be an effective treatment approach for patients with this disorder, and iii) ECT continues to be an effective treatment for patients who suffer depressive illness comorbid with PD and/or associated with the administration of DBS.

1. Laino C: Mild head injury may increase risk for parkinson disease. Neurol Today 2003; 3:1–7

2. Uryu K, Giasson BI, Longhi L, et al: Age-dependent synuclein pathology following traumatic brain injury in mice. Exp Neurol 2003; 184:214–224

3. Chou KL, Hurtig HI, Jaggi JL, et al: Electroconvulsive therapy for depression in a Parkinson’s disease patient with bilateral subthalamic nucleus deep brain stimulators. Parkinsonism Relat Disord 2005; 11:403–406

4. Kulisevsky J, Berthier ML, Gironell A, et al: Mania following deep brain stimulation for Parkinson’s disease. Neurology 2002; 59:1421–1424

5. Stefurak T, Mikulis D, Mayberg H, et al: Deep brain stimulation for Parkinson’s disease dissociates mood and motor circuits: a functional MRI case study. Mov Disord 2003; 18:1508–1516

6. Nayernouri T: Posttraumatic parkinsonism. Surg Neurol 1985; 24:263–264

7. Vila-Rodriguez F, McGirr A, Tham J, et al: Electroconvulsive therapy in patients with deep brain stimulators. J ECT 2014; 30:e16–e18

Background: Parents have large genetic and environmental influences on offspring’s cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Objective: We therefore examined human parent-offspring association in this neurocircuitry, and investigated the degree of association in gray matter volume between parent and offspring. Methods: We used voxel-wise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. Results: We found positive associations of regional gray matter volume in the corticolimbic circuit including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. Conclusion: The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression, and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations, and provide promising ways to investigate intergenerational transmission patterns in the human brain.

Background: Dementia with Lewy bodies (DLB) is characterized by progressive, reduced cognitive function accompanied by neuropsychiatric symptoms, including hallucination, delusion, and depressive symptoms. The hypersensitivity to antipsychotic agents is often linked to the difficulty in the treatment of the neuropsychiatric symptoms of DLB patients. Electroconvulsive therapy (ECT) could be given as a nonpharmacological option, but there are only a few studies about the efficacy and safety of ECT in DLB patients. Objective: This study aimed to assess the efficacy and safety of ECT in the treatment of neuropsychiatric symptoms with DLB. Methods: The inclusion criteria was following: 1) inpatients in Psychiatric Institute, Nara Medical University from December 2011 to August 2015; 2) was diagnosed as possible or probable DLB according to Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies; 3) showed depressive and/or psychosis-like symptom which was resistant to drug therapy referring for ECT; 4) aged 50 years or more. Six patients were recruited according to this criteria. We examined the efficacy and safety of ECT in these patients. The informed consent about the study was obtained from each subject before taking part in the study. Results: The present study showed a significant effect of ECT on depression and psychosis-like symptom of DLB and the possibility that ECT improved Parkinson symptom of DLB. Adverse events were not found during ECT sessions. Conclusion: Our results suggest that ECT could be an alternative tool as a nonpharmacological treatment for the neuropsychiatric symptoms of DLB patients.